Understanding motives for cannabis use is important for addiction prevention and intervention

Source: https://health.ucdavis.edu/news/headlines/teens-use-cannabis-for-coping-enjoyment/2023/12

11 December 2023

Source: https://doi.org/10.1038/d41586-023-03860-3

Source: https://www.conservativewoman.co.uk/roger-morgan-trump-must-clamp-marijuana-america-doomed/ October 2017

Abstract

Cannabis is harmful to the lungs, but in a different way to tobacco, causing significant respiratory symptoms such as bronchitis with evidence to suggest it can result in destructive lung disease – sometimes referred to as ‘bong lung’ – in heavy cannabis users.

These are the key findings from a review of research on the effects of smoking cannabis on the lungs undertaken by respiratory specialists, Professor Bob Hancox, from the University of Otago’s Department of Preventive and Social Medicine and Dr Kathryn Gracie, from Waikato Hospital’s Respiratory Department.

Cannabis is the second-most commonly smoked substance after tobacco and the most widely-used illicit drug world-wide. Although cannabis remains illegal in most countries, many countries – like New Zealand – are considering decriminalising or legalising its use.

Professor Hancox explains that much of the debate about legalising cannabis appears to revolve around the social and mental health effects. Both he and Dr Gracie believe policies around the liberalisation of cannabis should consider the wider health effects of smoking cannabis.

“The potential for adverse effects on respiratory health from smoking cannabis has had much less attention than the social and mental health effects,” Professor Hancox says.

“We believe policies around the liberalisation of cannabis should consider the potential impacts on the lungs.

“Whether liberalising availability will lead to further increases in cannabis use remains to be seen, but it is likely that patterns of cannabis use will change, with resulting health consequences.”

Because cannabis has been an illegal and unregulated substance and the fact most cannabis users also smoke tobacco, making the effects difficult to separate, Dr Gracie explains that it has been difficult to carry out research on cannabis and its direct impact on the lungs.

“Perhaps, most importantly, the individuals who are extremely heavy users of cannabis may not be well represented in the existing epidemiological research. Most case reports of cannabis-related destructive lung disease document very heavy cannabis consumption.

“Despite these limitations there is sufficient evidence that cannabis causes respiratory symptoms and has the potential to damage both the airways and the lungs.”

“Cannabis may also increase the risk of lung cancer, but there is not enough evidence to be sure of this yet,” Dr Gracie says.

Professor Hancox says there is still a lot to learn about cannabis, but there is sufficient evidence to show that smoking cannabis is not harmless to the lungs.

A combination of smoking both cannabis and tobacco is likely to result in poorer health outcomes.

“Many people smoke both cannabis and tobacco and are likely to get the worst of both substances.”

Source: https://www.otago.ac.nz/news/news/smoking-cannabis-causes-bronchitis-and-changes-to-lung-function May 2020

In 2017 Iceland received word-wide attention for having dramatically reversed the course of teenage substance use. From 1998 to 2018, the percentage of 15-16-year-old Icelandic youth who were drunk in the past 30 days declined from 42% to 5%; daily cigarette smoking dropped from 23% to 3%; and having used cannabis one or more times fell from 17% to 5%. The core elements of the model are: 1) long-term commitment by local communities; 2) emphasis on environmental rather than individual change; 3) perception of adolescents as social attributes. This presentation describes how the Iceland prevention model is built upon collaboration between policy makers, researchers, parent organizations, and youth practitioners. These groups have created a system whereby youth receive the necessary guidance and support to live fun and productive lives without reliance on psychoactive substances. The Model is being replicated in 35 municipalities within 17 countries around the globe. The Icelandic Model: Evidence Based Primary Prevention – 20 Years of Successful Primary Prevention Work was featured for the past two years at the Special Session of the United Nations General Assembly on the World Drug Problem.

Source: https://www.researchgate.net/publication/330347576_Perspective_Iceland_Succeeds_at_Preventing_Teenage_Substance_Use February 2019

US DRUG CZAR EXPLAINS CAUSES AND RSDT TOOL TO PREVENT TEEN DRUG USE AND OVERDOSE DEATH INTERVIEW WITH U.S. DRUG CZAR JOHN WALTERS

Introduction:  In response to recent news of a huge increase in drug overdose deaths and arrests for drug trafficking among Fairfax County youths, Fox News TV5 reporter Sherri Ly interviewed U.S. Drug Czar John Walters for his expert views on the cause and potential cure for these horrific family tragedies.  Following is a transcript of that half-hour interview with minor editing for clarity and emphasis added.  The full original interview is available through the 11/26/08 Fox5 News broadcast video available at link:

WALTERS:  Well, as this case shows, while we’ve had overall drug use go down, we still have too many young people losing their lives to drugs, either through overdoses, or addiction getting their lives off track.  So there’s a danger.  We’ve made progress, and we have tools in place that can help us make more progress, but we have to use them. 

Q 1:  You meet with some of these parents whose children have overdosed.  What do they tell you, and what do you tell them?

WALTERS:  It’s the hardest part of my job; meeting with parents who’ve lost a child.  Obviously they would give anything to go back, and have a chance to pull that child back from the dangerous path they were on.  There are no words that can ease their grief.  That’s something you just pray that God can give them comfort.  But the most striking thing they say to me though is they want other parents to know, to act.  And I think this is a common thing that these terrible lessons should teach us.

Many times, unfortunately, parents see signs: a change in friends, sometimes they find drugs; sometimes they see their child must be intoxicated in some way or the other.  Because it’s so frightening, because sometimes they’re ashamed – they hope it’s a phase, they hope it goes away – they try to take some half measures.  Sometimes they confront their child, and their child tells them – as believably as they ever can – that it’s the first time.  I think what we need help with is to tell people; one, it’s never the first time.  The probability is low that parents would actually recognize these signs – even when it gets visible enough to them – because children that get involved in drugs do everything they can to hide it.  It’s never the first time.  It’s never the second time.  Parents need to act, and they need to act quickly.  And the sorrow of these grieving parents is, if anything, most frequently focused on telling other parents, “Don’t wait: do anything to get your child back from the drugs.”

Secondly, I think it’s important to remember that one of the forces that are at play here is that it’s their friends.  It’s not some dark, off-putting stranger – it’s boyfriends, girlfriends.  I think that was probably a factor in this case.  And it’s also the power and addictive properties of the drug.  So your love is now being tested, and the things you’ve given your child to live by are being pulled away from them on the basis of young love and some of the most addictive substances on earth.  That’s why you have to act more strongly.  You can’t count on the old forces to bring them back to safety and health.

Q 2:  When we talk about heroin – which is what we saw in this Fairfax County drug ring, alleged drug ring – what are the risks, as far as heroin’s concerned?  I understand it can be more lethal, because a lot of people don’t know what they’re dealing with?

WALTERS:  Well it’s also more lethal because one, the drug obviously can produce cardiac and respiratory arrest.  It’s a toxic substance that is very dangerous.  It’s also the case that narcotics, like heroin – even painkillers like OxyContin, hydrocodone, which have also been a problem – are something that the human body gets used to.  So what you can frequently get on the street is a purity that is really blended for people who are addicted and have been long time addicted.  So a person who is a new user or a naïve user can more easily be overdosed, because the quantities are made for people whose bodies have adjusted to higher purities, and are seeking that effect that only the higher purity will give them in this circumstance.  So it’s particularly dangerous for new users.  But we also have to remember, it almost never starts with heroin.  Heroin is the culmination here.  I think some of the – and I’ve only seen press stories on this — some of these young people may have gotten involved as early as middle school.

We have tools so that we don’t have to lose another young woman like this– or young men.  We now have the ability to use Random Student Drug Testing (RSDT) because the Supreme Court has, in the last five years, made a decision that says it can’t be used to punish.  It’s used confidentially with parents.  We have thousands of schools now doing it since the president announced the federal government’s willingness to fund these programs in 2004.  And many schools are doing it on their own.  Random testing can do for our children what it’s done in the military, what it’s done in the transportation safety industry– significantly reduce drug use.

First, it is a powerful reason not to start.  “I get tested, I don’t have to start.”  We have to remember, it’s for prevention and not a “gotcha!”  But it’s a powerful reason for kids to say, even when a boyfriend or girlfriend says come and do this with me, “I can’t do it, I get tested.  I still like you, I still want to be your friend; I still want you to like me, but I just can’t do this,” which is very, very powerful and important.  And second, if drug use is detected the child can be referred to treatment if needed.

Q 3:  Is the peer pressure just that much that without having an excuse, that kids are using drugs and getting hooked?

WALTERS:  Well one of the other unpleasant parts of my job is I visit a lot of young people in treatment; teenagers, sometimes as young as 14, 15, but also 16, 17, 18.  It is not uncommon for me to hear from them, “I came from a good family.  My parents and my school made clear what the dangers were of drugs.  I was stupid.  I was with my boyfriend (or girlfriend) and somebody said hey, let’s go do this.  And I started, and before I knew it, I was more susceptible.”

We have to also understand the science, which has told us that adolescents continue to have brain development up through age 20-25.  And their brains are more susceptible to changes that we can now image from these drugs.  So it’s not like they’re mini-adults.  They’re not mini-adults.  They’re the particularly fragile and susceptible age group, because they don’t have either the experience or the mental development of adults.  That’s why they get into trouble, that’s why it happens so fast to them, that’s why it’s so hard for them to see the ramifications.

So what does RSDT do?  It finds kids early–­ if prevention fails.  And it allows us to intervene, and it doesn’t make the parent alone in the process.  Sometimes parents don’t confront kids because kids blackmail them and say “I’m going to do it anyway, I’m going to run away from home.”  The testing brings the community together and says we’re not going to lose another child.  We’re going to do the testing in high school – if necessary, in middle school.  We’re going to wrap our community arms around that family, and get those children help.  We’re going to keep them in school, not wait for them to drop out.  And we’re certainly not going to allow this to progress until they die.

Q 4:  And in a sense, if you catch somebody early, since you’re saying the way teenagers seem to get into drug use is a friend introduces it to a friend, and then next thing you know, you have a whole circle of friends doing it.  Are you essentially drying that up at the beginning, before it gets out of hand?

WALTERS:  That is the very critical point.  It’s not only helping every child that gets tested be safer, it means that the number of young people in the peer group, in the school, in the community that can transfer this dangerous behavior to their friends shrinks.  This is communicated like a disease, except it’s not a germ or a bacillus.  It’s one child who’s doing this giving it behaviorally to their friends, and using their friendship as the poison carrier here.  It’s like they’re the apple and the poison is inside the apple.  And they trade on their friendship to get them to use.  They trade on the fact that people want acceptance, especially at the age of adolescence.  So what you do is you break that down, and you make those relationships less prone to have the poison of drugs or even underage drinking linked to them.  And of course we also lose a lot of kids because of impaired driving.

Q 5:  And how does the drug testing program work, then, in schools– the schools that do have it.  Is it completely confidential?  Are you going to call the police the minute you find a student who’s tested positive for heroin or marijuana or any other illicit drug?

WALTERS:  That’s what is great about having a Supreme Court decision.  It is settled – random testing programs cannot be used to punish, to call law enforcement; they have to be confidential.  So we have a uniform law across the land.  And what the schools that are doing RSDT are seeing is that it’s an enormous benefit to schools for a relatively small cost.  Depending on where you are in the country, the screening test is $10-40.  It’s less than what you’re going to pay for music downloads in one month for most teenage kids in most parents’ lives.  And it protects them from some of the worst things that can happen to them during adolescence.  Not only dying behind the wheel, but overdose death and addiction.

 Schools that have done RSDT have faced some controversy; so you have to sit down and talk to people; parents, the media, young people.  You have to engage the community resources.  You’re going to find some kids and families that do have treatment needs.  But with RSDT you bring the needed treatment to the kids.

I tell, a lot of times, community leaders – mayors and superintendents, school board members – that if you want to send less kids into the criminal justice system and the juvenile justice system, drug test — whether you’re in a suburban area or in an urban area.

What does the testing do?  It takes away what we know is an accelerant to self-destructive behavior: crime, fighting in school, bringing a weapon, joining a gang.  We have all kinds of irrefutable evidence now – multiple studies showing drugs and drinking at a young age accelerate those things, make them worse, make them more violent, as well as increasing their risks of overdose deaths and driving under the influence.  So drug testing makes all those things get better.  And it’s a small investment to make everything else we do work better.

Again, drug testing is not a substitute for drug education or good parenting or paying attention to healthy options for your kid.  It just makes all those things work better.

Q 6:  And I know you’ve heard this argument before, but isn’t that big brother?  Aren’t there parents out there who say to you, “I’m the parent: why are you going to test my child for drugs in school; that’s my job?” 

WALTERS:  I think that is the critical misunderstanding that we are slowly beginning to change by the science that tells us substance abuse is a disease.  It’s a disease that gets started by using the drug, and then it becomes a thing that rewires our brain and makes us dependent.  So instead of thinking of this as something that is a moral failing, we have to understand that this is a disease that we can use the kind of tools for public health – screening and interventions – to help reduce it.

Look, let me give you the counter example.  It’s really not big brother.  It’s more like tuberculosis.  Schools in our area require children to be tested for tuberculosis before they come to school.  Why do they do that?  Because we know one, they will get sicker if they have tuberculosis and it’s not treated.  And we can treat them, and we want to treat them.  And two, they will spread that disease to other children because of the nature of the contact they will have with them and spreading the infectious agent.  The same thing happens with substance abuse.  Young people get sicker if they continue to use.  And they spread this to their peers.  They’re not secretive among their peers about it; they encourage them to use them with them.  Again, it’s not spread by a bacillus, but it’s spread by behavior.

If we take seriously the fact that this is a disease and stop thinking of it as something big brother does because it’s a moral decision that somebody else is making, we can save more lives.  And I think the science is slowly telling us that we need to be able to treat this in our families, for adults and young people.  We have public health tools that we’ve used for other diseases that are very powerful here, like screening – and that’s really what the random testing is.  We’re trying to get more screening in the health care system.  So when you get a check up, when you bring your child to a pediatrician, we screen for substance abuse and underage drinking.  Because we know we can treat this, and we know that we can make the whole problem smaller when we do. 

Q 7:  You have said there were about 4,000 schools across the country now that are doing this random drug testing.  What can we see in the numbers since the Supreme Court ruling in 2002, as far as drug use in those schools, and drug use in the general population?

WALTERS:  Well, what a number of those schools have had is of course a look at the harm from student drug and alcohol use.  Some of them have put screening into place, random testing, because they’ve had a terrible accident; an overdose death; death behind the wheel.  What’s great is when school districts do this, or individual schools do this, without having to have a tragedy that triggers it.  But if you have a tragedy, I like to tell people, you don’t have to have another one.  The horrible thing about a tragic event is that most people realize those are not the only kids that are at risk.

There are more kids at risk, obviously, in our communities in the Washington, DC area where this young woman died.  We know there’s obviously more children who are at risk of using in middle school and high school.  The fact is those children don’t have to die.  We cannot bring this young lady back.  Everybody knows that.  But we can make sure others don’t follow her.  And the way we can do that is to find, through screening, who’s really using.  And then let’s get them to stop – let’s work with their families, and let’s make sure we don’t start another generation of death.  So what you see in these areas is an opportunity to really change the dynamic for the better.

Q 8:  Now, although nationally drug use among our youth is going down – what does it say to you – when I look at the numbers specific to Virginia, the most recent that I could find tells me that 3% of 12th graders, over their lifetime, have used a drug like heroin?  What does it say to you?  To me, that sounds like a lot.

WALTERS:  Yeah, and it’s absolutely true.  I think the problem here is that when you tell people we are taking efforts that are making progress nationwide, they jump to the conclusion that that means that we don’t have a problem anymore.  We need to continue to make this disease smaller.  It afflicts our young people.  It obviously also afflicts adults, but this is a problem that starts during adolescence — and pre-adolescence in some cases — in the United States.  We can make this smaller.  We not only have the tools of better prevention but also better awareness and more recognition of addiction as a disease.  We need to make that still broader.  We need to use random testing.  If we want to continue to make this smaller, and make it smaller in a permanent way, random testing is the most powerful tool we can use in schools.

We want screening in the health care system.  We have more of that going on through both insurance company reimbursement and public reimbursement through Medicare and Medicaid for those who come into the public pay system.  That needs to grow.  It needs to grow into Virginia, it’s already being looked at in DC; it needs to grow into Maryland and the other states that don’t have it.  We are pushing that, and it’s relatively new, but it’s consistent with what we’re seeing – the science and the power of screening across the board.

We need to continue to look at this problem in terms of also continuing to push on supply.  We’re working to reduce the poisons coming into our communities, which is not the opposite of demand; that we have to choose one or the other.  They work together.  Keeping kids away from drugs and keeping drugs away from kids work together.  And where we see that working more effectively, we’ll save more lives.  So again, we’ve seen that a balanced approached works, real efforts work, but we need to follow through.  And the fact that you still have too many kids at risk is an urgent need.  Today, you have kids that could be, again, victims that you have to unfortunately tell about on tonight’s news, that we can save.  It’s not a matter we don’t know how to do this.  It’s a matter of we need to take what we know and make it reality as rapidly as possible.

Q 9:  Where are these drugs coming from?  Where’s the heroin that these kids allegedly got coming from?

WALTERS:  We do testing about the drugs to figure out sources for drugs like heroin.  Principally, the heroin in the United States today has come from two sources.  Less of it’s coming out of Colombia.  Colombia used to be a source of supply on the East Coast, but the Colombian government, as a part of our engagement with them on drugs, has radically reduced the cultivation of poppy and the output of heroin.  There still is some, but it’s dramatically down from what it was even about five years ago.  Most of the rest of the heroin in the United States comes from Mexico.  And the Mexican government, of course, is engaged in a historic effort to attack the cartels.  You see this in the violence the cartels have had as a reaction.  So we have promising signs.  There are dangerous and difficult tasks ahead, but we can follow through on that as well.

Most of the heroin in the world comes from Afghanistan; 90% of it.  And we are working there, of course, as a part of our effort against the Taliban and the forces of terror and Al Qaeda, to shrink that.  The good news is that last year we had a 20% decline in cultivation and a 30% decline in output there.  Most of that does not come here, fortunately.  But it has been funding the terrorists.  It’s been drained out of most of the north and the east of the country.  It’s focused on the area where we have the greatest violence today, in the southwest.  We’re working now – you see Secretary Gates talking to the NATO allies about bringing the counter-insurgency effort together with the counter-narcotics effort to attack both of these cancers in Afghanistan.  We have a chance to change heroin availability in the world in a durable way by being successful in Afghanistan.  We’ve started that path in a positive way.  Again, it’s a matter of following through as rapidly as possible.

Q 10:  Greg Lannes, the father of the girl in Fairfax County who died, told me that one of his main efforts, as you imagined, was to let people know that those drugs, they’re coming from where it is produced, outside our country; that they’re getting all the way down to the street level and into our neighborhoods– something that people don’t realize.  So when you hear that they busted a ring of essentially teenagers who have been dealing, using and buying heroin, what does that say to you as the man in charge of combating drugs in our country?

WALTERS:  Well again, we have tools that can make this smaller.  But we have to use those tools.  And we have multiple participants here.  Yes we need to educate.  And we need to make sure that parents know they need to talk to their children, even when their children look healthy and have come from a great home.  Drugs – we’ve learned, I think, over the last 25 years or more, drugs affect everybody; rich or poor, middle class, lower class or upper class.  Every family’s been touched by this, in my experience, by alcohol or drugs.  They know that reality– we don’t need to teach them that.

What we need to teach them is the tools that we have that they can help accelerate use of.  Again, I think – there is no question in my mind that had this young woman been in a school, middle school or high school that had random testing – since that’s where this apparently started, based on the information I’ve seen in the press – she would not be dead today.  So again, we can’t go back and bring her to life.  But we can put into place the kind of screening that makes the good will and obvious love that she got from her parents, the obvious good intentions that I can’t help but believe were a part of what happened in the school, the opportunities that the community has to have a lot of resources that she didn’t get when she needed them.  And now she’s dead.  Again, we can stop this: we just have to make sure we implement that knowledge in the reality of more of our kids as fast as possible.

Q 11:  Should anyone be surprised by this case?  And that such a hardcore drug like heroin is being used by young people?

WALTERS:  We should never stop being surprised when a young person dies.  They shouldn’t die.  They shouldn’t die at that young age, and we should always demand of ourselves, even while we know that’s sometimes going to happen today, that every death is a death too many.  I think that it is very important not to say we’re going to accept a certain level.  Never accept this.  Never!  That’s my attitude, and I know that’s the president’s  attitude as well here.  Never accept that heroin’s going to get into the lives of our teenagers.  Never accept that our children are going to be able to use and not be protected.  It’s our job to protect them.  They have a role, also, obviously in helping to protect themselves.  But we need to give them the tools that will help protect them.

When I talk to children and young adults in high school or college, they know what’s going on among their peers.  And in some ways, when you get them alone and they feel they can talk candidly, they tell us they don’t understand why we, as adults who say this is serious, don’t act.  They know that we see children who are intoxicated; they know that we must see signs of this, because as kid’s lives get more out of control, they show signs of it.  They want to know why we don’t act.

We can use the tools of screening, and we can use the occasion of a horrible event like this to bring the community together and say it’s time for us to use the shock and the sorrow for something positive in the future.  I haven’t met a parent of a child who’s been lost who doesn’t say I just want to use this now for something positive.  And that’s understandable, and I think we ought to honor that wish.

Q 12:  Well, I guess I’m not asking should we accept that this is in our schools, but is it naïve for people not to understand or realize that these hardcore drugs are in our schools, and in our communities, and in our neighborhoods. 

WALTERS:  Yeah.  Where it is naïve, I think, is to not recognize the extent and access that young people have to drugs and alcohol.  I think we sometimes think that because they come from a home where this isn’t a part of their lives now, that it’s not ever going to be part of their lives.  Look, your viewers should go on the computer.  Type marijuana into the Google search engine and see how many sites encourage them to use marijuana, how to get marijuana, how to grow marijuana, the great fun of marijuana.  Go on YouTube and type in marijuana, and see how many videos come up using marijuana, joking around about marijuana.  And then when you start showing one, of course the system is designed to show you similar things.  Type in heroin.  See what kind of sites come up, and see what kind of videos come up on these sites.  Young people spend more time on these sites than they do, frequently, watching television.  Remember, there is somebody telling your children things about drugs.  And if it’s not you, the chances are they’re telling them things that are false and dangerous.  So there is a kind of naiveté about what the young peoples’ world, as it presents itself to them, tells them about these substances.  It minimizes the danger, it suggests that it’s something that you can do to be more independent, not be a kid anymore. 

We, from my generation — because I’m a baby boomer — unfortunately have had an association of growing up in America with the rebellion that’s been associated with drug use.  That’s been very dangerous, and we’ve lost a lot of lives.  We have to remember that it’s alive and well, and has become part of the technological sources of information that young people have.  I also see young people in treatment centers who got in a chat room and somebody offered them drugs or offered them to come and buy them alcohol and flattered them, and got them involved in incredibly self-destructive behavior.  The computer brings every predator and every dangerous influence into your own child’s home – into their bedroom in some cases, if that’s where that computer exists.  You wouldn’t let your kids go out and play in the park with drug dealers.  If you have a computer and it’s not supervised, those drug dealers are in that computer.  Remember that.  And they’re only a couple of keystrokes away from your child.

Q 13:  And you talk about the YouTube and the computers and all those things.  What about just the overall societal image?  Because we have this whole image with heroin, of heroin chic.  How much does that contribute to the drug use, and how difficult does it make your job, when a drug is being made out to be cool in society by famous people?

WALTERS:  There are still some elements of that.  It was more prominent a number of years ago.  I would say you see less of that now glamorized in the entertainment industry, or among people who are celebrities in and out of entertainment.  You see more cases of real harm.  But it’s still out there.  The one place that I think is replacing that, just to get people ahead of the game here, is prescription pharmaceuticals.  Those have been marketed to kids on the internet as a safe high.  They falsely suggest that you can overcome the danger of an overdose because you can predict precisely the dosage of OxyContin, hydrocodone, Vicodin.  And there are sites that suggest what combination of drugs to use.  We’ve seen prescription drug use as the one counter example of a category of drug use going up among teens.  We’re trying to work on that as well, but that’s something that’s in your own home, because many people get these substances for legitimate medical care.  Young people are going to the medicine cabinet of family or friends, taking a few pills out and using those.  And those are as powerful as heroin, they’re synthetic opioids, and they have been a source of overdose deaths. 

So let’s not forget – while this Fairfax example reminds us of the issues of heroin chic and of the heroin that’s in our communities, the new large problem today is a similar dangerous substance in pill form in our own medicine cabinets.  Barrier to access is zero.  They don’t have to find a drug dealer; they just go find the medicine cabinet.  They don’t have to pay a dime for it because they just take it and they share that with their friends.  We need to remember, that’s another dimension here.  Keep these substances out of reach – under our control when we have them in our home.  Throw them away when we’re done with them.  Make sure we talk to kids about pills.  Because people, again, are telling them that’s the place to go to avoid overdose death, is to take a pill.

Q 14:  When you see a lot of these celebrities checking in and out of rehab, does it sort of glamorize it for kids?  And teach them hey, you can use, you can check into rehab, you can come back, you can – you know.  Is there a mixed message there?

WALTERS:  There is.  Some young people interpret it the way you describe; of it’s something you do and you can get away with it by going into rehab.  We do a lot of research on young people’s attitudes for purposes of helping shape prevention programs in the media, as well as in schools and for parents.  We do a lot with providing material to parents.  I would say that compared to where we’ve been in the last 15 or 20 years, there’s less glamorization today.

I think we should also remember the positive, because we reinforce that.  A lot of young people – obviously not all or we wouldn’t have this death – believe that taking drugs makes you a loser.  They’ve seen that a lot of those celebrities are showing their careers going down the toilet because they can’t get away from the pills and the drugs and the alcohol.  And I think they see that even among some of their peers.  That’s a good thing.  We should reinforce that as parents: teaching our kids that drug and alcohol use may be falsely presented to you as something you do that would make you popular, make you seem like you should have more status in society generally.  But actually, look at a lot of these people; they’ve had enormous opportunities, enormous gifts, and they can’t stop themselves from throwing them away.  And they may not stop themselves from throwing away their lives. 

I think you could use these events as a teachable moment.  It can go two ways.  Help your child understand what the truth is here.  And I tell young people – and I think parents have to start this more directly – this is the way this is going to come to you:  Somebody you really, really want to like you; somebody you really, really like; someone you may even love — or think you love — they’re going to say come and do this with me.  If you can’t find any other reason to not do this with them, say, “Before we do this, let’s go to a treatment center.  Let’s go talk to people who stood where we stood and said it’s not going to happen to me.”  If everybody, when they got the chance to start, thought of an addict or somebody who was dead, they wouldn’t start.  The fact is that does not enter their mind. 

Many people in treatment centers understand that part of the task of recovery is helping other people avoid this.  So they’re willing to talk about it.  In fact, that’s part of their path of staying clean and sober, which not many kids are going to be able to do on their own.  But it makes them think that what presents itself as something overwhelmingly attractive has behind it a horrible dimension, for their friends as well as for themselves.  And more and more, I think kids understand this.

We can use the science of this as a disease, and the experience of many families.  Remember, uncle Joe didn’t used to be like this.  Especially Thanksgiving, when we have families getting together and all of a sudden mom’s going to get loaded and become ugly in the corner.  We also have to remember we have an obligation to reach out to those people, and to get them help.  We can treat them.  Nobody gets sober, in my experience, by themselves.  They have to take responsibility.  But you have to overcome the pushback, and addiction and alcoholism have, as a part of the disease, denial.  When you tell somebody they have a problem, they get angry with you.  They don’t say hey thanks, I want your help.  They don’t hit bottom and become nice.  That’s a myth.  They need to be grabbed and encouraged and pushed.  Almost everybody in treatment is coerced – by a family member, by an employer, sometimes by the criminal justice system.

So remember that, when you find your child using and they want to lie to you up down and sideways saying, “It’s the first time I’ve ever done it.”  No, no, no, no, no, that’s the drugs talking.  That shows you, if anything, you have a bigger problem than you realized and you need to reach out, get some professional help.  But don’t wait!

Source:    National Institute of Citizen Anti-drug Policy (NICAP)

DeForest Rathbone, Chairman, Great Falls, Virginia, 703-759-2215, DZR@prodigy.net

Cannabis and cannabinoids are implicated in multiple genotoxic, epigenotoxic and chromosomal-toxic mechanisms and interact with several morphogenic pathways, likely underpinning previous reports of links between cannabis and congenital anomalies and heritable tumours. However the effects of cannabinoid genotoxicity have not been assessed on whole populations and formal consideration of effects as a broadly acting genotoxin remain unexplored. Our study addressed these knowledge gaps in USA datasets. Cancer data from CDC, drug exposure data from National Survey of Drug Use and Health 2003–2017 and congenital anomaly data from National Birth Defects Prevention Network were used. We show that cannabis, THC cannabigerol and cannabichromene exposure fulfill causal criteria towards first Principal Components of both: (A) Down syndrome, Trisomies 18 and 13, Turner syndrome, Deletion 22q11.2, and (B) thyroid, liver, breast and pancreatic cancers and acute myeloid leukaemia, have mostly medium to large effect sizes, are robust to adjustment for ethnicity, other drugs and income in inverse probability-weighted models, show prominent non-linear effects, have 55/56 e-Values > 1.25, and are exacerbated by cannabis liberalization (P = 9.67 × 10 –43 ,2.66 × 10 –15 ). The results confirm experimental studies showing that cannabinoids are an important cause of community-wide genotoxicity impacting both birth defect and cancer epidemiology at the chromosomal hundred-megabase level.

Source: https://www.nature.com/articles/s41598-021-93411-5.epdf July 2021

Nearly half of all U.S. citizens now live in a state where they can purchase cannabis from a recreational market, and all but 13 states have legalized medical use.  These state-level policies have all been developed and adopted under a federal prohibition, which may be changing soon as lawmakers in both the House and the Senate are developing federal proposals to legalize cannabis.

A new USC Schaeffer Center white paper shows how state-level cannabis regulations have weak public health parameters compared to other countries, leaving consumers vulnerable. Federal legalization is an opportunity to implement regulations that better protect consumers and promote reasonable use. Regulations policymakers should consider include placing caps on the amount of the main intoxicant (THC) allowed in products sold in the marketplace and placing purchase limits on popular high-potency cannabis products, like edibles and vape cartridges, as has been done in other legalized jurisdictions abroad.  

“Allowing the industry to self-regulate in the U.S. has generated products that are more potent and diverse than in other countries and has led to a variety of youth-oriented products, including cannabis-infused ice cream, gummies and pot tarts,” says Rosalie Liccardo Pacula, a senior fellow at the USC Schaeffer Center and Elizabeth Garrett Chair in Health Policy, Economics & Law at the USC Price School of Public Policy. “Current state regulations and public advisories are inadequate for protecting vulnerable populations who are more susceptible to addiction and other harm.”

High-potency cannabis products have been linked to short-term memory and coordination issues, impaired cognitive functions, cannabis hyperemesis syndrome, psychosis, and increased risks of anxiety, depression and dependence when used for prolonged periods. Acute health effects associated with high-potency products include unexpected poisonings and acute psychosis.

Policies should discourage excessive cannabis use

Product innovation within the legal cannabis industry has outpaced state regulations and our knowledge of health impacts of nonmedical, adult-use cannabis, write Pacula and her colleagues.  Cannabis concentrates and extracts can reach concentrated THC levels of 90% in certain cases – many, many times more potent than dried flower that ranges between 15-21%. These products are also increasingly popular – sales for concentrates like vape pens rose 145% during the first two years of legalization in Washington state.

But state approaches to regulation have insufficiently considered quantity and potency limits. Just two states, Vermont and Connecticut, have set potency limits on both flower and concentrates. Most states base sales limits on product weight and product type, an approach that allows individuals to purchase excessive amounts of high-potency products in a single transaction.

An individual in most states can purchase 500 10-milligram servings of concentrates in a single transaction. Six states allow purchases that exceed 1,000 servings. By comparison, a full keg of beer, which usually requires registration, provides 165 servings of alcohol.

“Voters in many of these states supported legalization because they were told we would regulate cannabis like alcohol, but in reality, when it comes to product innovation, contents and standard serving sizes, the cannabis market has largely been left on its own,” says Seema Pessar, a senior health policy project associate at the USC Schaeffer Center. “And that is what is concerning for public health.”

“We are seeing evidence of real health consequences from this approach, especially among young adults,” explains Pacula. For example, studies show a rise cannabis-related emergency department visits for acute psychiatric symptoms and cyclical vomiting in states that legalize recreational cannabis.

Key policies to support responsible cannabis use

To better regulate legal cannabis markets and products, researchers find four policy areas in which state laws and federal proposals can do more to encourage responsible use.

• Placing limits on the amount of THC in legal products sold: Setting clear and moderate caps on flower, concentrates and extracts.
• Instituting potency-based sales limits: Restricting the amount of cannabis that a retailer can sell to an individual in a single transaction or over a period of time, based on the THC amount in the product.
• Designing a tax structure based on the potency of products: Taxing cannabis in a manner similar to alcohol, based on intoxicating potential rather than by container weight or retail price.
• Implementing seed-to-sale data-tracking systems: Allowing regulatory agencies to view every gram of legal cannabis that is cultivated and watch it as it migrates throughout supply chain, including the comprehensive monitoring of ingredients added to products that are eventually purchased in stores.

While generating tax revenue and reversing damages from prohibition are important, so is prioritizing public health — and prolonged use of high-potency cannabis products has health consequences, the researchers write.

“It is difficult to implement restrictive health regulations in markets that are already operating, generating jobs and revenue,” Pacula says. “Now is when the federal government has the best chance of ensuring a market that fully considers public health.”

Source: Cannabis Regulations Inadequate Given Rising Health Risks of High-Potency Products – USC Schaeffer July 2022

Abstract

Drug Free America Foundation is launching its new digital advertisement campaign targeting viewers in Illinois. The digital animated ad is the second in a series titled “Marijuana…Know the Truth” and discusses the real dangers of marijuana use.  

As you know, Illinois is a state that is considering legalizing recreational marijuana this year. We hope this ad campaign will help address the misconceptions about the real dangers of marijuana use

This digital advertising campaign will utilize banner ads to drive viewers to our website where they can view the 2-minute ad. We are excited to say that through a generous donation, this campaign will provide over 10 million digital impressions in Illinois. We are hopeful that through additional donations, we are able to expand this campaign to other states and continue to spread the word on the dangers of marijuana.

Email from Drug Free America Foundation https://www.dfaf.org/ March 2019

Aaron Hernandez was supposed to be the epitome of the American Dream—overcoming childhood setbacks to earn a spot in the NFL on the New England Patriots. Millions of kids across America wish they could be so lucky. But the 2020 documentary on Netflix, “Killer Inside: The Mind of Aaron Hernandez,” takes a deep dive into his life to investigate how his dream unraveled into a nightmare. Convicted of murdering his friend Odin Lloyd and accused of killing two other men (but found not guilty), Hernandez took his own life in a prison suicide in 2017. He was only 27.
The compelling docuseries explores many of the factors that could have contributed to the tragic end of such a promising life—childhood abuse, unstable parenting, hidden bisexuality. And then there was his brain. The docuseries delivers a fascinating look at his troubled brain, but it misses one key factor that may have contributed to Hernandez’ brain dysfunction.

The Brain of Aaron Hernandez
After Hernandez’s death, his brain was delivered to Boston University, where researchers made razor-thin slices for examination. Their findings? His brain was “riddled” with Stage 3 chronic traumatic encephalopathy (CTE). This neurodegenerative disease, which has 4 stages, has been found in athletes like football players, boxers, and soccer players who endure repeated concussions and other blows to the head. It has been associated with memory loss, cognitive dysfunction, and suicidal thoughts and behavior.
A Boston University publication reported that Ann McKee, director of BU’s Chronic Traumatic Encephalopathy Center, said that his brain was the worst case of CTE ever seen in someone so young. “Especially in the frontal lobes, which are very important for decision-making, judgment, and cognition, we could see damage to the inner chambers of the brain,” she said. The frontal lobes are also involved in impulse control, empathy, and learning from past experiences.
The documentary focuses heavily on CTE and the significant role it likely played in Hernandez’ downfall, and for good reason. The filmmakers also hone in on another aspect of his life that may have contributed to his troubles—cannabis use. It is reported that the football player began smoking marijuana regularly in high school and continued to smoke throughout his pro career. The docuseries calls him a “chainsmoker” with a serious habit, but it neglects to connect the dots between marijuana use and brain dysfunction.

Marijuana and the Brain
A growing body of evidence shows that marijuana use impairs brain activity. In the largest known brain imaging study, which appeared in the Journal of Alzheimer’s Disease, scientists from Amen Clinics, Google, Johns Hopkins University, UCLA, and the UC San Francisco evaluated 62,454 brain SPECT scans of more than 30,000 individuals (ages 9 months to 105 years) to investigate factors that accelerate brain aging. SPECT (single-photon emission computed tomography) is a brain imaging technology that measures brain activity and blood flow. The study found that a number of brain disorders and behaviors predicted accelerated aging. Of all the disorders and behaviors analyzed, cannabis abuse ranked as the second-highest brain ager, topped only by schizophrenia.
The study, which included brain scans from 1,000 cannabis users, 25,168 non-cannabis users, and 100 healthy controls, showed reduced cerebral blood flow among the cannabis users compared to non-users and healthy controls. A significant decrease in blood flow was noted specifically in the right hippocampus, an area of the brain that helps with memory formation. This part of the brain is severely affected in those that suffer from Alzheimer’s disease.

Healthy SPECT Scan

Marijuana Affected SPECT Scan

Other research has concluded that marijuana harms the teenage brain in numerous ways. For example, a 2019 review found that it increases the risk of depression and suicidal thoughts and behaviors. And marijuana use at a young age has also been associated with increased impulsivity.
Although pot promoters would argue that most people who smoke marijuana don’t become murderers and don’t die by suicide, it’s important to understand that in vulnerable people it may have negative impacts on brain function that contribute to unhealthy behaviors. Sadly, considering that Hernandez’s brain was so damaged by CTE, marijuana use was likely only making bad brain function worse.

You Can Change Your Brain
Unfortunately, this information is too late to help Hernandez, but it isn’t too late for other football players who have endured years of helmet-to-helmet tackles. A study at Amen Clinics on 30 retired professional football players who had suffered head trauma showed that after following a brain healthy program for 6 months, 80% showed significant improvement in blood flow to the frontal lobes, as well as improvements in overall cognitive functioning, processing speed, attention, reasoning, and memory. Hall of Fame quarterback Terry Bradshaw spoke openly about his own brain rehabilitation after suffering multiple concussions. 
Likewise, it isn’t too late for people who grew up in traumatic households. See how a man named Kevin overcame his traumatic upbringing to enhance his brain health using a variety of innovative therapies. And it isn’t too late for people who have been bad to their brain with drug use. Find out how Arnie broke free from the chains of addiction. It’s never too late to start enhancing brain function.
The world’s largest database of brain scans related to behavior—over 160,000 and growing —shows that when you adopt a brain health program, you can change your brain and change your life for the better.
At Amen Clinics, we take a unique brain-body approach that gets to the root cause of your symptoms. Our comprehensive evaluations include brain SPECT imaging, as well as laboratory testing and assessing other important factors that could be contributing to symptoms. By getting to the root cause of your symptoms, we can create a more effective, personalized treatment plan for you.
If you want to join the tens of thousands of people who have already enhanced their brain health, overcome their symptoms, and improved their quality of life at Amen Clinics, speak to a specialist today at 888-288-9834. If all our specialists are busy helping others, you can also schedule a time to talk.

Source: What the Aaron Hernandez Documentary Missed About His Brain | Amen Clinics Amen Clinics February 2020

Abstract

Background:

Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure.

Objectives / Hypotheses:

Is cannabis associated with ASDI in USA? Is this relationship causal?

Methods:

Geospatio/temporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity.

Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse probability weighted (ipw) regressions.

Analysis conducted in R.

Results:

 ASDI rose nationally three-fold from 27.4 to 82.8 / 10,000 births 1991–2014 during a period when tobacco and alcohol abuse were falling but cannabis was rising. States including Nevada, Kentucky, Mississippi and Tennessee had steeply rising epidemics (Time: Status β-estimate = 10.72 (95%C.I. 8.39–13.05), P < 2.0 × 10 − 16). ASDI was positively related to exposure to cannabis and most cannabinoids.

Drug exposure data was near-complete from 2006 thus restricting spatial modelling from 2006 to 2014, N = 282. In geospatial regression models cannabis: alcohol abuse term was significant (β-estimate = 19.44 (9.11, 29.77), P = 2.2 × 10 − 4 ); no ethnic or income factors survived model reduction.

Cannabis legalization was associated with a higher ASDI (Time: Status β-estimate = 0.03 (0.01, 0.05), P = 1.1 × 10 -3). Weighted panel regression interactive terms including cannabis significant (from β-estimate = 1418, (1080.6, 1755.4), P = 7.3 × 10 -15). Robust generalized linear models utilizing inverse probability weighting interactive terms including cannabis appear (from β-estimate = 78.88, (64.38, 93.38), P = 1.1 × 10 -8).

Marginal structural models with machine-aided Super Learning association of ASDI with high v. low cannabis exposure R.R. = 1.32 (1.28, 1.36). Model e-values mostly > 1.5.

Conclusions:

ASDI is associated with cannabis use, frequency, intensity and legalization in a spatiotemporally significant manner, robust to socioeconomic demographic adjustment and fulfilled causal criteria, consistent with multiple biological mechanisms and similar reports from Hawaii, Colorado, Canada and Australia. Not only are these results of concern in themselves, but they further imply that our list of the congenital teratology of cannabis is as yet incomplete, and highlight in particular cardiovascular toxicology of prenatal cannabinoid and drug exposure.

Albert Stuart Reece and Gary Kenneth Hulse

Source:  BMC Pediatrics volume 20, Article number: 539 (2020) https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-020-02431-z November 2020

One way to deter harmful recreational drug use by teenagers is to treat them like adults. Rather than simply tell them to “Just Say No” to alcohol, tobacco or illicit drugs, it may be more helpful to explain how these substances create unique risks for them risks that arise due to the changing state of the adolescent brain.

It’s an approach recommended by Dr. Robert DuPont, the first director of the National Institute of Drug Abuse, the second White House “drug czar” and the current head of the Institute for Behavior and Health.

Scientists have long recognized that people who use alcohol, tobacco, marijuana and other drugs while adolescents are far more likely to use more dangerous drugs in their 30s and 40s. Back in 1984, researchers writing in the American Journal of Public Health reported that “the use of marijuana is a good predictor of the use of more serious drugs only if it begins early” and that early drinking is a similar “predictor of marijuana use.”

It should come as no surprise, then, that Americans in their 30s and 40s who used recreational drugs as teenagers are the group most severely affected by opioid overdoses today.

Unfortunately, neither the media nor popular culture adequately informs young people about the neurological damage alcohol, nicotine, and marijuana can inflict on the brain. On the contrary, despite strong evidence that early recreational drug use increases the likelihood of future drug addiction, the media and today’s culture often describe marijuana use as an “organic,” “natural” approach to anxiety and stress management. Indeed, Northern Michigan University launched the nation’s first medicinal plant chemistry major, offering students the chance to focus on marijuana-related studies. What message does that send to the still-developing minds of college students?

One group is taking a non-traditional approach to convincing students otherwise.

One Choice is a drug prevention campaign developed for teenagers by the Institute for Behavior and Health. It relies on cutting-edge neuroscience to encourage young Americans to make decisions that promote their brain health.

Pioneered by Dr. DuPont, One Choice specifically advocates that adolescents make “no use of any alcohol, nicotine, marijuana or other drugs” for health reasons. The theory is that adolescents who make the decision not to use alcohol, nicotine, or marijuana at all that make “One Choice” to avoid artificial, chemical brain stimulation are far less likely to wind up addicted to drugs such as opioids later on.

The One Choice approach is evidence-based. In 2017, scientists at Mclean Hospital and Harvard Medical School published their findings on the impact of early substance use on cognitive development. They explained that the brains of teenagers are still developing and can be negatively impacted by substance use. Adolescent brains are still forming the communication routes that regulate motivation, stress and habit-formation well into adulthood. As such, it is easier for substances to hijack and alter those routes in developing brains than in adult brains.

Hindering the vital attributes of habit formation, stress management and motivational behavior can drastically affect a young person’s academic performance. Collectively, and in the long run, that can impair the competitiveness of a national economy. Thus, it is crucial that young Americans learn to prioritize brain health.

The timing for the innovative One Choice approach is propitious. Today’s young Americans are more interested in biology, psychology and health sciences than ever before. According to the National Center for Education Statistics, the field of “health professions and related programs” is the second most popular major among college students, with psychology and biological or biomedical sciences following as the fourth and fifth most popular, respectively. By explaining developmental neuroscience to teenagers, One Choice engages young people on a topic of interest to them and presents the reality of a pressing public health issue, instead of throwing moral platitudes and statistics at them.

Pro-marijuana legalization organizations, such as the Drug Policy Alliance, agree: “The safest path for teens is to avoid drugs, doing alcohol, cigarettes, and prescription drugs outside of a doctor’s recommendations.” And certainly honesty, along with scientific accuracy, is critical if we are to persuade adolescents not to use drugs.

Brain health is critical to the pursuit of happiness. And leveraging scientifically accurate presentations and testimonies to convince young Americans to prioritize their own brain health early on can prevent future substance abuse.

Source: Using Neuroscience to Prevent Drug Addiction Among Teenagers | The Heritage Foundation January 2019

Just one or two joints seem to change the structure of the brain, say researchers from universities around the world, led by senior author and University of Vermont professor of psychiatry Hugh Garavan, PhD, and first author and former UVM postdoctoral fellow Catherine Orr, PhD.
 
The study is part of a long-term European effort called IMAGEN, which has collected brain images from 2,000 children in Ireland, France, and Germany, starting when they were age 14 and continuing through age 23.
 
Researchers compared the brain images of 46 children age 14 who reported having used marijuana once or twice with those of children that age who had not used the drug. The images of the marijuana triers showed greater brain volume in areas with cannabinoid receptors. The biggest differences were in the amygdala, involved in fear and other emotions, and the hippocampus, the site of memory development and spatial abilities.
 
“You’re changing your brain with just one or two joints. Most people would likely assume that one or two joints would have no impact on the brain,” says Dr. Garavan.
 
It is unclear what the extra gray matter in these brain areas means. Normally at age 14, the brain is refining its synaptic connections to make it thinner, not thicker. Dr. Garavan says one possibility is that initial marijuana use in this age group may be disrupting that “pruning” process.
 
The new findings open a new area of focus for future research.
 
Read study abstract here.

Source:  The Marijuana Report  16.01.2019

Abstract

The increasing use of marijuana by women of childbearing age raises a concern for potential adverse outcomes in the offspring (Ryan et al., 2018). There have been numerous studies of the consequences of maternal cannabis use in humans or Δ9-tetrahydrocannabinol (THC) administration during pregnancy in animals (Abel, 1980; Fried, 2002; Huizink, 2014; Trezza et al., 2008), but little or no attention has been paid to the role of paternal exposure for adverse consequences to the developing fetus or child. Animal studies where both males and females were exposed to THC in adolescence identified persistent changes in gene methylation in association with neurobehavioral anomalies in the offspring (Szutorisz and Hurd, 2018) ; however, these did not distinguish whether there was a specific paternal contribution, which would presumably involve epigenetic changes in sperm. Indeed, recent work found that cannabis exposure in humans, or THC exposure in rats, produces persistent changes in sperm DNA methylation, including the genes that were affected by combined paternal and maternal exposure, as well as genes associated with risk of autism spectrum disorder (Murphy et al., 2018; Schrott et al., 2020). The effects in rats were associated with long-lasting attentional impairment in the offspring (Levin et al., 2019).

In the present study, we provide one of the first demonstrations that paternal THC administration, prior to mating, results in abnormalities of offspring brain development, specifically targeting acetylcholine (ACh) systems, which provide essential inputs for learning, memory, reward, and mood. We exposed male rats for 28 days to THC at doses commensurate with moderate cannabis use in humans, mated them to drug-naïve females, and then assessed biomarkers of ACh synaptic function in the offspring. We conducted our evaluations longitudinally from adolescence through adulthood, so as to capture early and late stages of brain development and function, and made our assessments in brain regions comprising all the major ACh projections and their corresponding cell bodies. We evaluated the concentration of presynaptic high-affinity choline transporters (hemicholinium-3 [HC3] binding), the activity of choline acetyltransferase (ChAT), and the concentration of α4β2 nicotinic ACh receptors (nAChRs). High-affinity choline transporters and ChAT are both constitutive components of ACh nerve terminals but they differ in their regulatory mechanisms and hence in their functional significance. Choline acetyltransferase is the enzyme that synthesizes ACh, but is not regulated by nerve impulse activity, so that its presence provides an index of the density of ACh innervation (Slotkin, 2008). In contrast, HC3 binding to the choline transporter is directly responsive to neuronal activity (Klemm and Kuhar, 1979), so that comparative effects on HC3 binding and ChAT enable the characterization of both the concentration of ACh terminals and presynaptic impulse activity. We then calculated the HC3/ChAT ratio as an index of presynaptic activity relative to the number of cholinergic nerve terminals (Slotkin, 2008). Finally, the α4β2 nAChR is the most abundant subtype in the mammalian brain and regulates the ability of ACh systems to release other neurotransmitters involved in reward, cognition, and mood (Dani and De Biasi, 2001). These indices have been used successfully to characterize the impact of diverse neurotoxicants and diseases on ACh systems: neuroactive pesticides (Slotkin et al., 2013, 2019b), nicotine or tobacco smoke (Slotkin et al., 2015), polycyclic aromatic hydrocarbons (Slotkin et al., 2019a), and glucocorticoids (Slotkin et al., 2013); and terminal stages of Alzheimer’s disease (Slotkin et al., 1994).

Source: https://doi.org/10.1093/toxsci/kfaa004 February 2020

• Neither the cause of autism nor the effects of cannabis on a developing fetus are entirely clear 
• Researchers at the Ottawa Hospital and University of Ottawa studied 2,200 Canadian women who reported using marijuana while pregnant 
• The rate of autism among their children was four per 1,000 person-years, compared to 2.42 among children whose mothers did not use marijuana  

Pregnant women who smoke cannabis almost double the risk of their baby being born autistic, warns a new study.

By NATALIE RAHHAL ACTING US HEALTH EDITOR

Source: Autism is twice as common in children whose mothers used cannabis in pregnancy | Daily Mail Online

PUBLISHED 17:13, 10 August 2020

Cannabis use during pregnancy is associated with a host of negative outcomes.

Sondem/AdobeStock

The recent paper by Stanciu discussing cannabis use in pregnancy¹ makes several useful and highly salient points. With a more complete understanding of the published literature further important patterns in the data emerge. They aid our understanding of the pathobiology of in utero cannabis exposure and thereby powerfully inform the community on the most appropriate manner in which to regulate cannabis and cannabinoids from an improved evidence base.

It is well known that cannabis use has been liberalized across the United States as a result of well-financed and orchestrated campaigns.² Stanciu is correct that most epidemiological studies point towards harmful associations, that cannabis use in pregnancy is becoming more common, that it is widely recommended in pregnancy by cannabis dispensaries, and that increased rates of low birth weight, premature and stillbirths, and increased neonatal intensive care admission are well recognized associations. It is correct that all 4 longitudinal studies of children born after prenatal cannabis exposure (PCE) show increased adverse neurodevelopmental outcomes including impaired executive function, visuomotor processing deficits, heightened startle responses, impulse control, heightened susceptibility to addiction in later life, emotional behaviors, and motor defects.^3-5 Well-documented impacts on the glutamatergic, GABAergic and dopaminergic signaling in the brain are of concern as they represents major neurotransmitters in the central nervous system [CNS]. Well-established links between cannabis use and schizophrenia, bipolar disorder, anxiety, depression, and suicidal ideation are also correctly described. It is true that ACOG have made both historical and recent recommendations against its use in pregnancy, and these recommendations are relevant to practice in all medical specialties.

Conceptual and epidemiological extensions

While it is correct to observe that there is no described phenotype following PCE, it is also important to note that many of these neurodevelopmental deficits have been noted to overlap the ADHD and autism spectrum disorders. This is likely epidemiologically highly significant for the US, where autistic spectrum disorders have been shown to be growing exponentially.⁶ Cannabis use across the US was shown to be independently associated with autism rates across both time and space, to be dose-related⁶, and, based on conservative projections, has been predicted to be at least 60% higher in cannabis-legal states than in states where cannabis was illegal by 2030.⁷

A large Hawaiian study found an increased incidence of microcephaly (R.R. = 12.80, 95%C.I. 4.13-36.17)⁸ and the CDC have twice reported elevated rates of anencephalus (adjusted O.R. 1.7, C.I. 0.9-3.4) and (posterior O.R. 1.9 (C.I. 1.1, 3.2).^9,10 This sets up a clear spectrum of severity from mild neurodevelopmental impairment, to microcephaly, to anencephalus and then fetal death. In the context of dose-response relationships and strong geotemporospatial associations issues of causality necessarily arise.

Stanciu’s observation that preclinical studies in experimental animals are important to understand the likely effects of PCE in individuals, not least due to the problem of the frequent exposure to multiple substances clinically, is also correct. This issue was studied in detail long ago in the 1960s and 1970s, and succinctly summarized by Graham’s telling observation: “oedema, phocomelia, omphalocoele, spina bifida, exencephaly, multiple malformations including myelocoele. This is a formidable list.”¹¹

However, a reasonable question might be: “Why don’t we see such a broad teratological spectrum clinically?”

Stanciu’s remark that there are “no overt birth defects” is an oft-repeated myth and is in error, as well as obviously being at odds with several preclinical studies, especially in the most predictive species for human teratology (ie, hamsters and white rabbits).^12,13

A recent paper from the Centers for Disease Control (CDC) noted that 4 defects, anencephalus, gastroschisis, diaphragmatic hernia and esophageal atresia were more common following PCE.⁹ The American Academy of Pediatrics (AAP) and the American Heart Association (AHA) issued a joint position statement that both ventricular septal defect (VSD) and Ebsteins anomaly were also elevated by PCE.¹⁴

The review of 17 years of birth defects from Hawaii found 21 defects to be elevated after PCE and featured prominently cardiovascular defects (atrial septal defect (ASD), VSD, hypoplastic left heart syndrome, tetralogy of Fallot (ToF) and pulmonary valve atresia or stenosis), chromosomal defects such as Downs syndrome, body wall defects such as gastroschisis, limb defects including syndactyly and upper limb reduction defects, facial, bowel and genitourinary system defects with calculated rate ratios ranging from 5.26 (C.I. 1.08-15.46) to 39.98 (C.I. 9.03-122.29).⁸

In September and October 2018 Colorado released 2 datasets of congenital anomalies across the period of its cannabis legalization program from 2000 to 2013 and 2000 to 2014 and reported 87,772 and 64,463 major defects respectively (which are obviously contradictory).¹⁵ Based on 4830 and 4026 major anomalies in the year 2000 this represents a case excess of 20,152 (29.80%) or 11,753 anomalies (22.30%) respectively. During this period the use of tobacco and alcohol was declining and other drug use was not rising. Only cannabis use rose. Importantly, models quartic in time indicated a non-linear response of total birth defects to rising cannabinoid exposure. Estimated exposure to several cannabinoids including cannabinol, THC, and tetrahydrocannabivarin was shown to be positively associated with major defect rates and to be robust to adjustment for other drug use. CNS defects (microcephalus, neural tube defects), cardiovascular defects (ASD, VSD, patent ductus arteriosus (PDA)), total chromosomal anomalies including Downs syndrome, musculoskeletal, respiratory and genitourinary anomalies all rose dramatically.

Defects described as being cannabis-related (by the Hawaiian, CDC, AAP and AHA investigators) rose more quickly than cannabis-unrelated defects (P<0.003). As fetal cardiac tissue and the central great vessels have high numbers of cannabinoid receptors from early in fetal life it is easy to understand why this pattern might emerge. Since ASD, VSD and PDA are the most common cardiovascular congenital anomalies it is understandable that total cardiovascular anomalies increased in Colorado.

A recent review of total congenital anomalies in Canada showed that they were 3 times more common in the northern territories which consume more cannabis, and that these effects were robust to adjustment for other drug exposure and for socioeconomic variables.¹⁶ Total cardiovascular defects, Downs syndrome and gastroschisis were noted prominently in this series. Neural tube defects including anencephalus and spinal bifida and meningomyelocoele were falling across Canada from 1991 to 2007, although it was not clear whether the decline was due to dietary folate supplementation or increased antenatal early termination of pregnancy for anomalies (ETOPFA).¹⁷ Notwithstanding this it was recently shown that within each of 3 periods (the pre-folate period, the transitional period and the post-folate period) neural tube defects across Canada were becoming more common.¹⁷

An Australian dataset found greatly elevated relative rates of cardiovascular (PDA, ASD, VSD, ToF, transposition of great vessels), body wall (gastroschisis, exomphalos, diaphragmatic hernia), chromosomal (Downs syndrome, Turners syndrome, Edwards Syndrome (trisomy 18)), genitourinary, hydrocephalus, neural tube defects, and bowel defects with borderline results for anencephalus (ETOPFA data unavailable) in a high cannabis use area in Northern New South Wales compared to Queensland state-wide data.¹⁸

Transposition of the great vessels was previously linked with paternal cannabis exposure.¹⁹

The presence of Downs syndrome on the list of cannabis-associated anomalies in Hawaii, Colorado, Canada and Australia is important as it necessarily implies megabase-scale genetic damage.^8,15,16,18 Since cannabis interferes with tubulin metabolism and thus the separation of the chromosomes which occurs in mitotic anaphase it is easy to see how PCE-induced chromosomal mis-segregation errors might occur.²⁰ Studies of PCE in rodents show that cannabis induces major alterations of gene expression widely with 8% alteration in DNA sperm methylation patterns, changes which are transmissible to subsequent F1 generations.²¹

Stanciu’s comment about a so-called “cannabis phenotype” is provocative. It is true that a “fetal cannabis syndrome” (FCS) has not been described in the way that a “fetal alcohol syndrome” (FAS) has. Fetal alcohol syndrome of course is a very diverse and pleomorphic group of clinical presentations and a wide spectrum of presentations is described. Importantly the fetal alcohol has been described as being mediated by the cannabinoid type 1 receptor (CB1R’s) and is mediated epigenetically.^22-26 The suggestion that alcohol can work epigenetically via CB1Rs but cannabinoids cannot defies the bounds of credulity. Moreover, as noted above, there is as yet no objective marker of gestational cannabinoid exposure. Once such a biomarker has been derived (say epigenetically and / or glycomically²⁷) then an objective measure will exist to allow genotype-epigenotype-phenotype correlative studies to be performed so that we can usefully investigate if a fetal cannabis syndrome phenotype spectrum might exist. However, if researchers do not believe it might exist then it is clear that one will not be described. It is our view that once an objective biomarker is established it will only be a matter of time before a diverse and highly variable FCS is also defined and enters the clinical diagnostic compendium.

Recent US data and analysis

CDC publish 5-year averaged birth defect data for many states as part of the National Birth Defects Prevention Network (NBDPN) annual reports which can be combined with Substance Abuse and Mental Health Services Administration (SAMHSA) state and substate data to examine nationwide drug-related trends. ETOPFA rates are taken from historical time series.

Figure 1A charts Downs syndrome rates corrected for estimated ETOPFA rates against cannabis exposure. Both rates are elevated (shown as pink and purple) in Colorado, Oregon, Washington, Alaska, Maine and Massachusetts.

Downs Syndrome By Cannibas Use

Figure 1B shows the relationship of Downs syndrome to cigarette use for this year which is very different.

Downs Syndrome By Cigarette Use

The Figure also shows the Downs syndrome rates by cannabis use quintile for both the raw Downs syndrome rates (Figure 1C) and the ETOPFA-corrected data (Figure 1D). One notes not only a rising trend with cannabis use, but also an abrupt jump from the fourth to the fifth quintile.

Downs Syndrome Rate by Quintiles of Cannabis Use

This jump is seen when many defects are analyzed in this manner. A list of defects would include, but would not be limited to: atrial septal defect, atrioventricular septal defect, cleft lip and / or palate (all forms combined), trisomy 21 (Downs syndrome), Turners syndrome and ventricular septal defect.

Downs Syndrome by Quintiles of Cannabis Use (ETOPFA-CORRECTED)

Figure 2 lists the prevalence ratio of 62 congenital anomalies tracked by the National Birth Defect Prevention Network (NBDPN) in quintile 5 versus lower quintiles and notes that 44 of them are significantly elevated in the highest quintile of cannabis using states.

Prevalence Ratios

Literature-wide limitations

It should be noted in passing that most of these studies suffer from several major common limitations. Many of the defects described are disorders for which ETOPFA is commonly practiced and frequently recommended to pregnant patients. ETOPFA data was generally not available to investigators. It is beyond question that were such data included the findings would be of greater magnitude and of even greater concern. Secondly many studies rely on self-report which is subject to recall-bias and may be misled. Patients who use cannabis early in pregnancy but stop after they are informed of their pregnant status might answer “no” to questions of PCE, but in fact their fetus is exposed prenatally due to the prolonged terminal half-life of excretion of cannabinoids from body fat stores. Hence a reliable biomarker is required to properly define the denominator in these studies, but it is not thought to exist at present. It could however easily be derived from epigenomic and/or glycomic studies.²⁷

Thirdly there are major analytical limitations of the described series. Advanced analytical methods that allow data analysis simultaneously across both space and time exist and are called geospatial or spatiotemporal techniques. The CDC has demonstrated ability to track congenital anomalies by county. Application of geospatial techniques to county data is therefore possible and would be well assisted by the provision of cannabis-exposure data from the SAMHSA 395 substate areas. Methods which allow the investigation of apparently causal relationships, including inverse probability weighting and the calculation of E-values to quantify unmeasured confounding have similarly not been deployed in this field.

These deficits in the literature represent major gaps in our knowledge which may readily be addressed by the application of available techniques to currently extant data and thus vastly augment the evidence base for well-informed policy formulation. Our group is presently addressing this major knowledge gap with a series of papers on these and related subjects utilizing geospatiotemporal regression, the formal techniques of causal inference, and multiple imputation of chained equations to complete CDC data for various congential anomalies and heritable childhood cancers where such data is missing or withheld for specific ethnic minorities.

Extensive presently unpublished analyses from our group extend the United States analyses presented in preliminary and embryonic form in Figure 1 and Figure 2 using geotemporospatial and causal inference techniques with strongly confirmatory results for both state-based spatiotemporal association and in several cases causal links.

Concluding thoughts

In broad overview the patterns which emerge from these major population-based studies of cannabis-related human teratology indicate several findings that are remarkable for their consistency across series originating from Hawaii, Colorado, Canada, and Australia and for their exact and precise concordance with very worrying data in experimental animals. Prominent amongst affected organ systems includes the CNS, CVS and chromosomal disorders. Body wall and limb defects also likely follow the endovascular cannabinoid receptor distribution pattern, and this is consistent with current understandings related to the pathogenesis of gastroschisis and limb embryogenesis which are both thought to be primarily vasculocentric. Similarly, in the genitourinary and gastrointestinal systems, peripheral cannabinoid receptors are widely distributed and appear from as early as 12 weeks of fetal life. Dose-response effects are seen in many of the above analyses which is one of the major criteria of Hill’s causal algorithm. The sequence of severity of CNS defects (neurodevelopmental impairments/autism-microcephaly-anencephaly-foetal death) also implies a gradation of phenotypic effects of PCE.

The PCE literature has widespread limitations including its reliance on self-report data, the general non-availability of ETOPFA data, the lack of reliable biomarkers to define exposure, and the pointed absence of state-of-the-art analytical techniques including high-resolution geotemporospatial analysis and the formal techniques of causal inference assessment.

Given these limitations the concordance with preclinical and mechanistic data and the positive and highly consistent associations that have been demonstrated in several jurisdictions are particularly concerning. They carry far-reaching genotoxic and intergenerational implications and argue powerfully against cannabis legalization.

Dr Reece is practice principal at Southcity Family Medical Centre and Professor of Medicine at University of Western Australia and Edith Cowan University. Dr Hulse is Professor of Addiction Medicine within the Division of Psychiatry at The University of Western Australia and the Faculty of Health Sciences at the Edith Cowan University. Neither author has any conflicts of interest to declare.

Source:  https://www.psychiatrictimes.com/view/cannabis-pregnancy-rejoinder-exposition-cautionary-tales   October 2020

There is evidence in both patients with psychotic disorders and the general population that cannabis use is associated with adverse effects of psychopathology and cognition.

RESEARCH UPDATE

Substance use comorbidity in schizophrenia has been described as “the rule rather than the exception.”¹ The large Epidemiological Catchment Area study estimated that 47% of patients with schizophrenia also had a lifetime comorbid diagnosis of a substance use disorder.² Substance use comorbidity is also often deleterious to the course of schizophrenia, including potential contributions to medication non-adherence and illness relapse.¹ Cannabis (marijuana) is one of the most commonly used substances by patients with schizophrenia.

There is recent, renewed interest in the endocannabinoid system, which represents a novel potential treatment target in schizophrenia.³ Modulation of this system by the main psychoactive component in marijuana, Δ9-tetrahydro-cannabinol (THC), can induce acute psychosis and cognitive impairment. However, the non-psychotropic plant-derived agent cannabidiol (CBD) may decrease psychotic symptoms and improve cognitive function in schizophrenia.^4-6

Presently, CBD oil is sold at numerous shops throughout the US, with purported benefits that include alleviation of symptoms such as depression, anxiety, insomnia, and pain. However, the purity and safety of CBD is not regulated by the US Food and Drug Administration. CBD may be “contaminated” with some amount of THC and/or other unknown ingredients. In the past decade, there have been a number of systematic reviews regarding associations between cannabis use and psychosis. Therefore, a review of systematic evidence for associations between cannabis use, risk of psychosis, and the clinical course of schizophrenia is of particular relevance to the practicing clinician.

Adverse effects of cannabis on psychosis and cognition

There is evidence from a quantitative review of 15 studies in healthy participants that a single administration of THC (intravenous, oral, or nasal) versus placebo induced positive, negative, and other psychopathology with large effect sizes (ESs).⁷ Furthermore, evidence from 69 studies, comprising 2152 adolescents and young adults who used cannabis and 6575 controls with minimal cannabis exposure, showed that frequent or heavy use was associated with significantly reduced cognitive functioning with a small-to-medium ES = -0.25, although these effects were diminished with abstinence for more than 72 hours.⁸

Cannabis use and risk of psychosis

Moore and colleagues⁹ performed a systematic review of 35 studies of cannabis use and risk of psychotic mental health outcomes. They found that individuals who had used cannabis had a significant, 1.4-fold increased risk of any psychotic outcomes, independent of potential confounding and transient intoxication effects. Findings also provided evidence for a dose-response effect, with even greater, 2.1-fold risk in individuals who used cannabis most frequently.

More recently, Marconi and colleagues¹⁰ performed a meta-analysis of 10 studies, including 66,810 individuals, that investigated the association between the degree of cannabis consumption and risk of psychosis. In all individual studies, higher levels of cannabis use were associated with increased risk of psychosis. They also found evidence for a dose-response relationship, with a 2-fold increase in risk for the average cannabis user, and a 4-fold increase in risk for the heaviest users, compared with non-users. Although these findings do not definitively establish a causal association between marijuana use and psychotic disorders, it nevertheless remains a replicated risk factor for psychosis with a clear dose-dependent relationship.

Cannabis use in patients with psychotic disorders

Koskinen and colleagues¹¹ performed a quantitative review of the rates of cannabis use disorders (CUDs) in clinical samples of patients with schizophrenia. They identified 35 studies for inclusion in the meta-analysis. The median current rate of CUD was 16.0% (Interquartile Range [IQR] 8.6-28.6%), and the median lifetime rate of CUD was 27.1% (IQR=12.2-38.5). The rate of current/lifetime CUDs was markedly higher in first-episode (28.6%/44.4%) versus chronic schizophrenia (22.0%/12.2%), as well as in younger patient samples and samples with a high proportion of males. They concluded that approximately 1 in 4 patients with schizophrenia has a diagnosis of a comorbid CUD.

Hunt and colleagues¹² more recently performed a systematic review of the prevalence of comorbid substance use in patients with schizophrenia spectrum disorders. They identified 69 studies, and the pooled estimate for current or lifetime CUD was 26.2%. Consistent with the review by Koskinen and colleagues,¹¹ the prevalence was significantly higher in individuals with first-episode psychosis (35.6%) versus chronic schizophrenia (20.8%), but did not differ by study setting or patient clinical status.

The substantial prevalence of cannabis use also appears to extend to the psychosis prodrome. There is evidence from 30 studies, including 4205 individuals at ultra high risk (UHR) for psychosis, that there are high rates of current (26.7%) and lifetime (52.8%) cannabis use, and CUDs (12.8%).¹³ Compared with non-users, UHR cannabis users also had higher rates of suspiciousness and unusual thought content.

Furthermore, research suggests that people with substance-induced psychoses will later transition to a diagnosis of schizophrenia. Murrie and colleagues¹⁴ synthesized the results of longitudinal observations studies of transition from substance-induced psychosis to schizophrenia. Six studies with estimates of transition to schizophrenia among 3040 people with cannabis-induced psychosis were included. The risk of transition to schizophrenia in these individuals was 34% (95% CI 25-46%), which was the highest risk among all substances. They concluded that substance-induced psychoses are common reasons for seeking care, and these serious conditions are associated with substantial risk of transition to schizophrenia. Treatment of cannabis-induced psychoses should be considered in the same framework as that for other brief psychotic disorders (i.e., engagement, assessment, and care); this also may help decrease rates of transition to schizophrenia.

Impact of cannabis on psychotic disorders

Large and colleagues¹⁵ conducted a systematic review of the association between cannabis use and the age of onset of psychosis. They included 41 samples, finding that the age of onset of psychosis for those who used cannabis was 2.7 years younger than for non-users, corresponding to a small-to-medium effect size of 0.41. These findings are broadly consistent with a potential causal role for cannabis in the development of psychosis in some patients.

Bogaty and colleagues¹⁶ performed a meta-analysis of 14 studies of neurocognition in lifetime cannabis users and never-users in young patients with psychotic disorders (aged 15 to 45 years). They found that lifetime cannabis users performed significantly worse than never-users on several cognitive domains, including premorbid and current IQ, verbal learning and working memory, and motor inhibition. Effect sizes were small to medium for most domains (0.17-0.40), except for verbal working memory, which showed a large effect size (0.76). Interestingly, patients who use cannabis performed better on tests of conceptual set-shifting. Increasing age exacerbated the between-group differences.

Schoeler and colleagues¹⁷ conducted a systematic review and meta-analysis of the effect of continued versus discontinued cannabis use after the onset of psychosis. They identified 24 studies, including 16,565 patients with pre-existing psychosis and at least a 6 month duration of follow-up. They found that continued cannabis use was associated with a significant: increase in risk of relapse of psychosis compared with non-users (ES=0.36) and discontinued users (ES=0.28); longer hospital admissions than non-users (ES=0.36); and more severe positive, but not negative, symptoms. Krause and colleagues¹⁸ performed a meta-analysis of the efficacy, acceptability, and tolerability of antipsychotics in patients with schizophrenia and comorbid substance use. They included 8 randomized controlled trials in patients with cannabis use comorbidity. Clozapine was superior to other antipsychotics for reduction of substance use and negative symptoms in those who used cannabis. Risperidone was superior to olanzapine for reducing of drug cravings and weight gain.

Conclusions

Premorbid cannabis use is associated with a dose-dependent increased risk of developing a psychotic disorder. There is evidence in both patients with psychotic disorders and the general population that cannabis use is associated with adverse effects of psychopathology and cognition. Cannabis use and CUDs are highly prevalent throughout the clinical course of illness.

Cannabis use is associated with an earlier age of onset of psychosis and more severe impairments in neurocognition. Continued cannabis use after the onset of psychosis is associated with increased risk of illness relapse, longer hospitalizations, and more severe positive psychopathology. There is also evidence for superior efficacy of clozapine for reduction of substance use and negative symptoms in patients with schizophrenia and comorbid cannabis use. Targeted interventions for improved prevention, detection, and treatment are warranted to improve outcomes in this population.

Dr Miller is Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for Psychiatric Times.

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

Source: https://www.psychiatrictimes.com/view/novel-insights-cannabis-psychosis July 2020

Research suggests that smoking marijuana carries many of the same cardiovascular health hazards as smoking tobacco.

Credit…Gracia Lam

Do you have the heart to safely smoke pot? Maybe not, a growing body of medical reports suggests.

Currently, increased smoking of marijuana in public, even in cities like New York where recreational use remains illegal (though no longer prosecuted), has reinforced a popular belief that this practice is safe, even health-promoting.

“Many people think that they have a free pass to smoke marijuana,” Dr. Salomeh Keyhani, professor of medicine at the University of California, San Francisco, told me. “I even heard a suggestion on public radio that tobacco companies should switch to marijuana because then they’d be selling life instead of selling death.”

But if you already are a regular user of recreational marijuana or about to become one, it would be wise to consider medical evidence that contradicts this view, especially for people with underlying cardiovascular diseases.

Compared with tobacco, marijuana smoking causes a fivefold greater impairment of the blood’s oxygen-carrying capacity, Dr. Keyhani and colleagues reported.

In a review of medical evidence, published in January in the Journal of the American College of Cardiology, researchers described a broad range of risks to the heart and blood vessels associated with the use of marijuana.

The authors, led by Dr. Muthiah Vaduganathan, cardiologist at Brigham and Women’s Hospital in Boston, point out that “marijuana is becoming increasingly potent, and smoking marijuana carries many of the same cardiovascular health hazards as smoking tobacco.”

Edible forms of marijuana have also been implicated as a possible cause of a heart attack, especially when high doses of the active ingredient THC are consumed.

With regard to smoking marijuana, Dr. Vaduganathan explained in an interview, “The combustion products a tobacco smoker inhales have a very similar toxin profile to marijuana, so the potential lung and heart effects can be comparable. When dealing with patients, we really have to shift our approach to the use of marijuana.”

His team reported, “Although marijuana is smoked with fewer puffs, larger puff volumes and longer breath holds may yield greater delivery of inhaled elements.” In other words, when compared to tobacco smoking, exposure to chemicals damaging to the heart and lungs may be even greater from smoking marijuana.

Dr. Vaduganathan said he was especially concerned about the increasing number of heart attacks among marijuana users younger than 50. In a registry of cases created by his colleagues, in young patients suffering a first heart attack, “marijuana smoking was identified as one factor that was more common among them.” The registry revealed that, even when tobacco use was taken into account, marijuana use was associated with twice the hazard of death among those under age 50 who suffered their first heart attack.

Other medical reports have suggested possible reasons. A research team headed by Dr. Carl J. Lavie of the John Ochsner Heart and Vascular Institute in New Orleans, writing in the journal Missouri Medicine, cited case reports of inflammation and clots in the arteries and spasms of the coronary arteries in young adults who smoke marijuana.

Another damaging effect that has been linked to marijuana is disruption of the heart’s electrical system, causing abnormal heart rhythms like atrial fibrillation that can result in a stroke. In one survey of marijuana smokers, the risk of stroke was increased more than threefold.

These various findings suggest that a person need not have underlying coronary artery disease to experience cardiovascular dysfunction resulting from the use of marijuana. There are receptors for cannabinoids, the active ingredients in marijuana, on heart muscle cells and blood platelets that are involved in precipitating heart attacks.

Cannabinoids can also interfere with the beneficial effects of various cardiovascular medications, including statins, warfarin, antiarrhythmia drugs, beta-blockers and calcium-channel blockers, the Boston team noted.

The researchers found that in an analysis of 36 studies among people who suffered heart attacks, the top three triggers were use of cocaine, eating a heavy meal and smoking marijuana. And 28 of 33 systematically analyzed studies linked marijuana use to an increased risk of what are called acute coronary syndromes — a reduction of blood flow to the heart that can cause crushing chest pain, shortness of breath or a heart attack.

“In settings of an increased demand on the heart, marijuana use may be the straw on the back, the extra load that triggers a heart attack,” Dr. Vaduganathan said. He suggested that the recent decline in cardiovascular health and life expectancy among Americans may be related in part to the increased use of marijuana by young adults.

“We should be screening and testing for marijuana use, especially in young patients with symptoms of cardiovascular disease,” Dr. Vaduganathan urged.

He expressed special concern about two recent practices: the vaping of marijuana and the use of more potent forms of the drug, including synthetic marijuana products.

“Vaping delivers the chemicals in marijuana smoke more effectively, resulting in increased doses to the heart and potentially adverse effects that are more pronounced,” the cardiologist said. “Marijuana stimulates a sympathetic nervous system response — an increase in blood pressure, heart rate and demands on the heart that can be especially hazardous in people with preexisting heart disease or who are at risk of developing it.”

Dr. Vaduganathan’s team estimated that more than two million American adults who say they have used marijuana also have established cardiovascular disease, according to data from the National Health and Nutrition Examination Surveys in 2015 and 2016.

According to Dr. Keyhani, who works at the San Francisco VA Medical Center, the combination of marijuana smoking and pre-existing heart disease is especially concerning because inhaling particulate matter of any kind can harm the heart and blood vessels.

“Marijuana is a leafy green, and combustion of any plant is probably toxic to human health if the resulting products are inhaled,” she explained. “Unfortunately, the research base is inadequate because marijuana hasn’t been studied in randomized clinical trials.”

A major problem in attempts to clarify the risks of marijuana is its classification by the U.S. Drug Enforcement Administration as a Schedule I drug, making it illegal to study it rigorously in controlled clinical trials.

Scientists must then resort to the next best research method: prospective cohort studies in which large groups of people with known habits and risk factors are followed for long periods to assess their health status. “The challenge is to recruit a cohort of daily cannabis users,” Dr. Keyhani said. “It’s absolutely important to look at the health effects of cannabis now that the prevalence of daily use is increasing. The absence of evidence is not evidence of absence.”

While there are currently no official guidelines, Dr. Vaduganathan’s team urged that anyone known to be at increased risk of cardiovascular disease should be advised to minimize the use of marijuana or, better yet, quit altogether.

Source:  https://www.nytimes.com/2020/10/26/well/live/marijuana-heart-health-cardiovascular-risks.html October 2020

Abstract

Accidental paediatric cannabis poisonings are an incidental effect of cannabis use. The average THC content of cannabis resin and the number of consumers are rising sharply in the USA and in most European countries. The objective is to study the evolution of prevalence and severity of paediatric exposures to cannabis in France.

Method

This is a retrospective observational study of cases detected by French poison centers between January 1^st 2010 and December 31^st 2017 of cannabis exposure by ingestion in children aged ten or younger. The clinical severity was assessed using the Poisoning Severity Score (PSS). The criteria used for assessing the overall severity were as follows: PSS ≥ 2, admission to paediatric intensive care, coma and respiratory depression (univariate and multivariate logistic regression).

Results

A total of 965 cases of poisoning were covered. The annual average number of cases was 93 between 2010 and 2014 and 167 between 2015 and 2017. The median age was 15 months (range, 6 months–10 years) and the sex ratio was 1:1. The form of cannabis ingested was mainly resin (75%). During the period covered by the study, 26.1% of children (n = 252) presented with a PSS ≥ 2, 4.5% (n = 43) coma, 4.6% (n = 44) with respiratory depression and 11.7% (n = 113) were admitted into paediatric intensive care (out of 819 hospitalizations). No fatal cases were reported. In comparison to the 2010–2014 period, the length of hospital stays was significantly higher (p < 0.0001) and the comas were significantly deeper (lower score on the Glasgow coma scale, p < 0.005) in 2015–2017. Following adjustments made for the sex, age and weight of the children, the data show that the severity of the poisonings was significantly greater in 2015–2017 in terms of PSS score, the number of comas and monitoring in intensive care (p < 0.001).

Conclusion

The data indicates a significant increase in the number of cases of paediatric exposure to cannabis and a rise in the seriousness of poisonings between 2010 and 2017.

Source:  https://www.tandfonline.com/doi/abs/10.1080/15563650.2020.1806295 June 2020

A new study recently published in Nature Medicine found a stunning association between prenatal THC exposure and development of autism. Using provincial birth registries, Canadian researchers analyzed all live births that occurred in Ontario between April 2007 and March 2012 for a total of 497,821 births.

Investigators found that infants who were prenatally exposed to THC were 57% more likely to develop autism spectrum disorder (ASD) and 35% more likely to develop intellectual disabilities and learning disorders. Previous studies of this type have been difficult to interpret due to polysubstance use among expectant mothers making it difficult to tease out the effects of THC exposure alone. In this study, researchers were able to directly compare unexposed infants to those whose mothers only used marijuana during their pregnancy. Thus, any effects observed in this study can be reliably attributed to prenatal THC exposure since no other substances were used. Results persisted even adjusting for other potential risk factors for ASD such as maternal age, education, psychiatric disorders, socioeconomic status, parity, and race.

The results of this study confirm that of previous research on the harms of prenatal THC exposure. Nevertheless, marijuana is routinely recommended to pregnant women by pot docs as well as dispensary employees with no medical training at all. Given the explosion in marijuana use among pregnant women in states like FL, lawmakers must take immediate action to fund education campaigns and ban marijuana recommendations for pregnant women. How many more lives need to be ruined so that Big Pot and their political allies can line their pockets?

Source:  https://www.dfaf.org/study-finds-link-between-prenatal-thc-exposure-and-autism/ 19.08.20

ABSTRACT

Parental cannabis use has been associated with adverse neurodevelopmental outcomes in offspring, but how such phenotypes are transmitted is largely unknown. Using reduced representation bisulphite sequencing (RRBS), we recently demonstrated that cannabis use is associated with widespread DNA methylation changes in human and rat sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation (p < 0.05) at 17 CpG sites in human sperm. We successfully validated the differential methylation present in DLGAP2 for nine CpG sites located in intron seven (p < 0.05) using quantitative bisulphite pyrosequencing. Intron 7 DNA methylation and DLGAP2 expression in human conceptal brain tissue were inversely correlated (p < 0.01). Adult male rats exposed to delta-9-tetrahydrocannabinol (THC) showed differential DNA methylation at Dlgap2 in sperm (p < 0.03), as did the nucleus accumbens of rats whose fathers were exposed to THC prior to conception (p < 0.05). Altogether, these results warrant further investigation into the effects of preconception cannabis use in males and the potential effects on subsequent generations.

KEYWORDS: Cannabis, sperm, DNA methylation, autism, heritability

Introduction

Cannabis sativa is the most commonly used illicit psychoactive drug in the United States (U.S.) and Europe [¹]. In the U.S., 11 states and Washington D.C. have legalized the recreational use of cannabis and 33 states have legalized the use of medicinal cannabis [²,³]. Since 1995, cannabis potency (defined as the concentration of the psychoactive cannabis component delta-9-tetrahydrocannabinol, or THC, in the sample [⁴]) has consistently risen from ~4% to as high as 32% in some states [²,⁵,⁶]. Changes in cannabis potency have been accompanied by changes in attitudes about cannabis and patterns of cannabis use. Between 2002 and 2014, the percentage of adults in the U.S. who perceived cannabis use as risky declined from 50% to 33% [⁶]. During this same period, the percentage of U.S. adults who believed cannabis to have no risk rose from 6% to 15% [⁶]. According to a 2015 Survey on Drug Use and Health, 52.5% of men in the U.S. of reproductive age (≥18) have reported cannabis use at some point in their lives, making cannabis exposure especially relevant for potential future fathers [⁷–¹¹].

Given the increased prevalence of cannabis use in the U.S., studies are beginning to focus on the effects of use on the health and development of offspring. Prenatal cannabis exposure via maternal use during pregnancy is associated with decreased infant birth weight, an increased likelihood to require the neonatal intensive care unit, and the potential for an impaired fetal immune system compared to those infants who are not exposed during gestation [¹,¹²]. In rodent studies, rat pups born to parents who were both exposed to THC during adolescence had increased heroin-seeking behaviour later in life, a phenotype that was accompanied by epigenetic changes in the nucleus accumbens [¹³–¹⁵]. These studies and others have begun to highlight the potential for intergenerational consequences of cannabis exposure [¹⁶]. Identifying the mechanism that underlies these changes is critical as cannabis use continues to increase across the U.S.

The environment impacts the integrity and maintenance of the epigenome such that it is now viewed as a molecular archive of past exposures [¹⁷]. While the majority of environmental epigenetic studies are focused on the impact of the inutero environment on the epigenome and health of the child, it has become apparent that the exposure history of the father must also be considered – specifically the impact of his exposures on the sperm epigenome. Studies have shown that exposure to phthalates, pesticides, nutritional deficiencies, and obesity can all induce potentially heritable changes in the sperm epigenome [¹⁸–²⁴]. It is likely that other common and emerging exposures, including cannabis, may also contribute to disruption of sperm DNA methylation in a similar fashion, and that such changes could be transmitted to the subsequent generation.

Using reduced representation bisulphite sequencing (RRBS) our group recently demonstrated that cannabis use in humans, and THC exposure in rats, is associated with decreased sperm concentrations and widespread changes in sperm DNA methylation [²⁵]. Of the regions identified in humans, Discs-Large Associated Protein 2 (DLGAP2) exhibited significant hypomethylation in the sperm of cannabis-exposed men compared to controls (p < 0.05). DLGAP2, a membrane-associated protein located in the post-synaptic density of neurons, plays a key role in synapse organization and neuronal signaling [²⁶]. Dysregulation of DLGAP2 is associated with various neurological and psychiatric disorders, such as autism spectrum disorder (ASD) and schizophrenia [²⁶–²⁹]. In our prior screen, we identified 17 differentially methylated CpG sites within DLGAP2 in the sperm of cannabis-exposed men compared to controls. DLGAP2 was just one of 46 genes with greater than 10 CpG sites showing significantly altered DNA methylation in the sperm of cannabis users compared to controls, out of the 2,077 genes we identified as having altered DNA methylation. The first objective of this study was to validate our preliminary RRBS findings for DLGAP2 using quantitative bisulphite pyrosequencing. Our second objective was to determine the functional association between DNA methylation and gene expression of DLGAP2 to better understand how cannabis use might affect this relationship. To determine the possible intergenerational effects of paternal cannabis use, our third objective was to determine if Dlgap2 was differentially methylated in the sperm of rats exposed to THC versus controls, and if so, whether or not these changes were intergenerationally heritable.

Results

DLGAP2 is hypomethylated in sperm from cannabis users versus controls by Reduced Representation Bisulphite Sequencing (RRBS)

Our prior study [²⁵] revealed 17 differentially methylated sites by RRBS in the sperm of cannabis users compared to controls for the DLGAP2 gene. Table S1 lists all 17 of these sites and their genomic coordinates. ^{Figure 1a} graphically demonstrates the significant hypomethylation of nine of these sites that are clustered together in the seventh intron of this gene. DLGAP2 is schematically shown in ^{Figure 1b}, including the exon-intron structure, position of CpG islands, transcription start site and the region of interest in intron 7 within the context of the gene body, with an inset showing the nucleotide sequence analysed in this study.

Validation of DLGAP2 RRBS methylation data

To confirm the methylation differences that were initially detected using RRBS, we designed a bisulphite pyrosequencing assay for the DLGAP2 intron 7 region (see ^{Figure 1b}) which captures 10 CpG sites, nine of which were identified as significantly differentially methylated using RRBS. We first validated pyrosequencing assay performance using defined mixtures of fully methylated and unmethylated human genomic DNAs. The measured levels of methylation by pyrosequencing showed good agreement between the amount of input methylation levels and the amount of methylation detected (r² = 0.99 and p = 0.0003) (^{Figure 1c}). These results confirmed the linearity of the assay in the ability to detect increasing amounts of DNA methylation at this region across the full range of possible methylation values, and indicate that the assay is suitable for use with biological specimens.

The DLGAP2 intron 7 region is not an imprinting control region (ICR)

DLGAP2 is paternally expressed in the testis, biallelically expressed in the brain, and has low expression elsewhere in the body [³⁰]. Since DLGAP2 is known to be genomically imprinted in testis [³⁰], and since the imprint control region for this gene has not yet been defined, we sought to determine if the region of interest in intron 7 is part of the DLGAP2 imprint control region (ICR). The methylation at ICRs is established during epigenome reprogramming in the primordial germ cells in embryonic development. Male and female gametes exhibit divergent methylation at ICRs, and this methylation profile is maintained through subsequent post-fertilization epigenetic reprogramming and in somatic cells throughout the life course. Therefore, we expected that if the DLGAP2 intron 7 region is an ICR, the diploid testis tissues from human conceptuses would exhibit approximately 50% methylation due to the complete methylation of one allele at this region and the complete lack of methylation at the other allele. Human conceptal testes tissues (n = 3) showed an average of 72.5% methylation at the DLGAP2 intron 7 region (^{Figure 1d}). This finding, of higher than anticipated and variable levels of methylation, is inconsistent with ICR status.

Bisulphite pyrosequencing validates the RRBS methylation data in human sperm

We next performed quantitative bisulphite pyrosequencing on the same sperm DNA samples from cannabis users and controls as those used to generate the RRBS data to confirm the loss of methylation present at the intron 7 region of DLGAP2. All nine CpG sites that were hypomethylated in the cannabis users by RRBS were also found to be hypomethylated by bisulphite pyrosequencing, as well as an additional CpG site that was captured in the assay design (p < 0.05 for all 10 sites) (^{Figure 2}). Following Bonferroni correction of the p value to adjust for multiple comparisons (p < 0.005), CpG sites 1,2,3,5,7,8,9, and 10 remained significant. From this pyrosequencing assay we observed methylation differences of 7–15% between the sperm of the cannabis users (n = 8) compared to controls (n = 7). Correlation of the RRBS and pyrosequencing data for each individual CpG site showed significant agreement at all sites analysed (p < 0.02 for all sites; Figure S1). All CpG sites showed a significant loss of methylation in accordance with the direction of change observed by RRBS for these same CpG sites.

Methylation of DLGAP2 intron 7 is inversely correlated with DLGAP2 expression

Given that we observed significant loss of intron 7 DLGAP2 DNA methylation in sperm of cannabis users relative to non-users, we next examined the relationship between DNA methylation and gene expression in the brain, where this gene’s function is critical. We used 28 conceptal brain tissues to examine the relationship between DNA methylation and mRNA expression. Expression levels were normalized to the lowest expressing sample, and the relationship between DNA methylation and mRNA expression was calculated with a Pearson correlation. We found that as methylation increased in this region, mRNA expression decreased significantly (p < 0.05) (^{Figure 3a}). Knowing that there are sex differences in autism spectrum disorder (ASD), and that dysregulation of DLGAP2 is associated with ASD [²⁶], we sought to determine if there were any sex differences in the methylation-expression relationship in these tissues. To investigate this, we ran the correlation for males (n = 15) and females (n = 13) independently. The inverse relationship between methylation and expression was evident for both males and females, but this relationship was significant only in females (p = 0.006) (^{Figure 3b, c}).

Intergenerational inheritance of altered Dlgap2 DNA methylation

We next sought to investigate Dlgap2 using data obtained from our prior study [²⁵] to determine if there was any differential methylation of Dlgap2 in THC versus control rats that was not initially identified using the imposed thresholds of that study. We were particularly interested in the potential for intergenerational transmission and to determine if route of THC exposure affected DNA methylation at this gene. The pilot study rats [²⁵] were given THC via oral gavage (to mimic oral ingestion of drug) while subsequent studies dosed rats via intraperitoneal injection (to mimic inhalation of drug). From the rats administered THC via oral gavage versus controls, we identified a region of Dlgap2 that showed differential methylation by the RRBS analysis that contains eight CpG sites. This region is in the first intron of Dlgap2, in a CpG island that spans the first exon of this gene as well (schematic of the gene structure and sequence of this region shown in ^{Figure 4a}). We validated the rat Dlgap2 pyrosequencing assay using commercially available rat DNA of defined methylation status. The results showed good agreement between the input methylation and the amount of methylation detected by pyrosequencing (r² = 0.92, p = 0.01) (^{Figure 4b}).

We were able to demonstrate intergenerational inheritance of an altered DNA methylation pattern in Dlgap2. Comparing the average methylation for exposed and unexposed sperm for each CpG site revealed that sites 2,3,4 and 6 of the eight CpG sites analysed were significantly hypomethylated in the sperm of rats exposed via injection to 4mg/kg THC compared to controls (p = 0.03 to p = 0.005) (^{Figure 4c}). CpG site 6 remained significant after Bonferroni correction (p < 0.006). The same region of Dlgap2 was then analysed in the hippocampus and nucleus accumbens of rats whose fathers were exposed to control or 4mg/kg THC. While CpG site 7 was significantly hypomethylated (p < 0.05) in the hippocampus of the offspring (^{Figure 5a}), this site was not identified as differentially methylated in the sperm of THC exposed rats, and therefore we could not conclude that this change was transmitted as the result of changes present in the exposed sperm. In the nucleus accumbens, however, significant hypomethylation (p = 0.02) at CpG site 2 was detected in the offspring (^{Figure 5b}), one of the same sites identified in the sperm of THC exposed rats. We also found that there was an inverse relationship between DNA methylation and expression of Dlgap2 in the nucleus accumbens, though not statistically significant likely due to the small sample size available in this study (n = 6 exposed, n = 8 unexposed; Figure S2).

Discussion

In this study, we examined the effects of regular male cannabis use on human sperm DNA methylation, at DLGAP2. Our RRBS study initially identified 17 CpG sites in DLGAP2 that were differentially methylated in the sperm of cannabis users compared to controls. Of the sites that were initially identified, nine of them all reside together in the seventh intron of this gene, though not in a defined CpG island. To first confirm the RRBS data, we performed quantitative bisulphite pyrosequencing for the nine clustered CpG sites. We were able to capture an additional CpG site with careful assay design for a total of ten CpG sites analysed via bisulphite pyrosequencing. We successfully validated the RRBS findings, confirming that there was significant hypomethylation among these ten sites with cannabis use. We confirmed a significant inverse correlation between methylation and expression at this region in human conceptal brain tissues.

To begin to determine whether or not the effects of cannabis on sperm are heritable, we analysed sperm from THC exposed and control male rats, as well as the hippocampus and nucleus accumbens from offspring of THC exposed and control males for changes in DNA methylation at Dlgap2. Rats exposed to THC were given a dose (4mg/kg THC for 28 days) that is pharmacodynamically equivalent to daily cannabis use to resemble frequent use in humans. We identified significant hypomethylation at Dlgap2 in the sperm of exposed rats as compared to controls. This hypomethylated state was also detected in the nucleus accumbens of rats born to THC exposed fathers compared to controls, supporting the potential for intergenerational inheritance of an altered sperm DNA methylation pattern. While the changes in the degree of methylation are small in the rats (0.5–0.7%), we previously reported that fractional changes in methylation can significantly influence the degree to which the gene’s expression is altered [³¹].

DLGAP2 is a member of the DLGAP family of scaffolding proteins located in the post-synaptic density (PSD) of neurons. The PSD is a protein-dense web that lies under the postsynaptic membrane of neurons and facilitates excitatory glutamatergic signaling in the central nervous system [²⁶,³²]. DLGAP2 functions to transmit neuronal signals across synaptic junctions and helps control downstream signaling events [²⁶,³²]. Due to its important role in PSD signaling, even small changes in the expression of DLGAP2 can have severe consequences [²⁶,³²]. Of particular relevance, DLGAP2 has been linked to schizophrenia and importantly, has been identified as an autism candidate gene [²⁷,²⁸,³³,³⁴]. Differential methylation of DLGAP2 is reported in the brain of individuals with autism, and has been linked to post-traumatic stress disorder in rats [²⁷,³⁵]. Knockout of Dlgap2 in mice results in abnormal social behaviour, increased aggressive behaviour, and learning deficits [³⁶].

Studies are increasingly showing associations between cannabis use and various neuropsychiatric and behavioural disorders including anxiety, depression, cognitive deficits, autism, psychosis, and addiction [²,⁶,⁷,⁹,¹⁴,³⁷–³⁹]. Research looking into the effects of THC exposure found that rat pups born to parents who were exposed to THC during adolescence showed increased effort to self-administer heroin compared to those born to unexposed parents [¹³]. This increase in addictive behaviour was driven by THC-induced changes in DNA methylation, occurring in the striatum, including the nucleus accumbens [¹⁴,¹⁵]. One of the genes whose methylation was altered by parental THC exposure was Dlgap2 [¹⁵]. Recently, a group from Australia analysed datasets from two independent cohorts to examine the relationship between cannabis legalization in the U.S. and ASD incidence. They determined there was a strikingly significant positive association between cannabis legalization and increased ASD incidence. Further, the study authors predicted that there will be a 60% increase in excess ASD cases in states with legal cannabis by 2030, and deemed ASD the most common form of cannabis-associated clinical teratology [⁴⁰].

It is estimated that the ratio of boys with ASD to girls with ASD is 4:1 which led us to stratify our analysis looking at the relationship between DNA methylation and gene expression by sex [⁴¹,⁴²]. The results of our methylation-expression analyses demonstrated a significant association in females but not males. While we don’t know the ASD status of these samples, there are several reasons why this may be the case. First, there are certain genes that confer a stronger ASD phenotype in girls compared to boys [⁴¹,⁴²]. Thus, while we see the trend in both sexes, it is possible that dysregulation of this gene may manifest phenotypically more in girls. Alternatively, it may be that the regulatory relationship between methylation and expression is retained in females while altered methylation further exacerbates an already fragile relationship in males. Overall, this data confirms that the region of DNA methylation within DLGAP2 that was differentially methylated in the sperm of cannabis users compared to controls is functionally important in the brain.

DLGAP2 is an imprinted gene that exhibits paternal expression in the testis, biallelic expression in the brain, and low expression elsewhere in the body [³⁰]. Because the methylation established at imprinted genes resists post-fertilization epigenetic reprogramming [⁴³–⁴⁵], this supports the possibility that changes in methylation at DLGAP2 in sperm could be transmitted to the next generation. However, given that the region in intron 7 is not an ICR, it is unlikely that this would be a potential mechanism for intergenerational inheritance of an altered methylation pattern at this region. However, it has recently been discovered that a subset of genes termed ‘escapees’ are able to escape primordial germ cell (PGC) and post-fertilization reprogramming events [⁴⁶,⁴⁷], providing a mechanism for epigenetic changes incurred by sperm to be passed on to the subsequent generation.

Processes in the PSD are sensitive to endocannabinoids [²⁶,⁴⁸–⁵¹], which suggests that these processes are potentially sensitive to exogenous cannabinoids, such as THC and cannabis. This is especially important as cannabis legalization and use are increasing dramatically across the U.S. It is estimated that 22% of American adults currently use cannabis, of which 63% are regular users (≥1–2 times per month) [⁷–¹⁰]. Among regular users 55% are males and over half of all men over 18 have reported cannabis use in their lifetime [⁷–¹⁰]. Importantly, this age range includes individuals of reproductive age. Since almost half of all pregnancies in the U.S. are unplanned, there is concern that many pregnancies may occur during a time when one, or both, parents are using or are exposed to cannabis [⁵²].

Our results provide novel findings about the effects of paternal cannabis use on the methylation status of an ASD candidate gene, a disorder whose rates continue to climb, but whose precise aetiologies remain unknown. Studies are beginning to show that there is a potential for paternal intergenerational inheritance. In particular, epigenetic changes in umbilical cord blood of babies born to obese fathers were also found in the sperm of obese men. This study is the first to demonstrate that there are changes present in the sperm epigenome of cannabis users at a gene involved in ASD.

The results of this study have several limitations. The sample size was small, which might limit generalization of the study findings. However, even though our sample size was small, we were able to identify common pathways that were differentially methylated in both human and rat sperm, highlighting the potential specificity of these effects [²⁵]. We did not account for a wide variety of potential confounders such as various lifestyle habits, sleep, diet/nutrition, exercise, etc, given that their influence on the sperm DNA methylome is largely unknown. Larger studies are required to confirm these findings. In the conceptal tissues we were only able to analyse whole brain, rather than the areas where DLGAP2 is most highly expressed such as the hippocampus and the striatum, which could have diluted the strength of the results.

Strengths of the study included that we used a highly quantitative method to confirm the methylation status that was measured by RRBS. This study was the first demonstration of the association between cannabis use and substantial hypomethylation of DLGAP2 in human sperm. Additionally, we are able to confirm a functional relationship between methylation and expression in a relevant target tissue, and have shown that the relationship between methylation and expression is weakened in males, which could bear relevance to the sexual dimorphism in the prevalence of autism. This is the first demonstration of potential heritability of altered methylation resulting from preconceptional paternal THC exposure. Given the increasing legalization and use of cannabis in the U.S., our results underscore a need for larger studies to determine the potential for heritability of DLGAP2 methylation changes in the human F1 generation and beyond. It will also be important to examine how cannabis-associated methylation changes relate to neurobehavioral phenotypes

Source:   Epigenetics. 2020; 15(1-2): 161–173.

Published online 2019 Aug 26. doi: 10.1080/15592294.2019.1656158

To Whom it may concern

On behalf of Drug Free Australia and our coalition of drug prevention researchers, we wish to commend to you, research that could well be a game-changer in informing and preventing a large proportion of Australia’s substance use issues.

The research is in various stages of development and a synopsis of current and emerging research, being done by Dr Stuart Reece and Professor Gary Hulse should be of genuine interest for all Australian Health Professionals. However, it appears that, to date, too many of the world’s researchers have placed this important research in the ‘too hard’ basket, similar to the way the NHS in the United Kingdom did with research into Pandemics.

At present the COVID-19 pandemic and how it is being addressed, should be a ‘wakeup call’ to Australian health authorities that prevention is the single most important goal. A ‘Harm Minimisation’ only approach, fails to achieve best-practice primary prevention outcomes. The passive discounting of the primary pillar of the National Drug Strategy – Demand Reduction over the last 30 years (and particularly the last 10) has seen a very large increase in illegal drug use in this nation.

The only exception to this has been seen in the correct and full use of both demand and supply reduction on the drug Tobacco. There has been little or no use of harm reduction mechanisms and a relentless and unified approach to abstinent/cessation modelling and it has worked spectacularly well, seeing Australia with, arguably, the lowest daily tobacco use in the world.

The research, that we now summarise, should not be placed in Australia’s ‘too hard’ basket. Rather, it warrants recognition by all Australian Health authorities for the world break-through that it is. Such evidence-based data offers timely insights that should promote and resource primary prevention and demand reduction.

Synopsis of the research:
1. Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis Albert Stuart Reece, MBBS(Hons), FRCS(Ed), FRCS(Glas), FRACGP, MD(UNSW), and Gary Kenneth Hulse, BBSc(Hons), MBSc, PhD
https://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Canadian_Cannabis_Consumption_and_Patterns_of.99248.aspx

Status
Mapping showed cannabis use was more common in the northern Territories of Canada in the Second National Survey of Cannabis Use 2018. Total congenital anomalies, all cardiovascular defects, orofacial clefts, Downs syndrome and gastroschisis were all found to be more common in these same regions and rose as a function of cannabis exposure.

When Canada was dichotomized into high and low cannabis use zones by Provinces v Territories the Territories had a higher rate of total congenital anomalies 450.026 v 390.413 (O.R.=1.16 95%C.I. 1.08-1.25, P=0.000058; attributable fraction in exposed 13.25%, 95%C.I. 7.04–19.04%). In geospatial analysis in a spreml spatial error model cannabis was significant both alone as a main effect (P<2.0×10-16) and in all its first and second order interactions with both tobacco and opioids from P<2.0×10-16.

Conclusion:

These results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down’s syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity.

The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada’s northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate further research.

139 References – click on this link to access.
https://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Canadian_Cannabis_Consumption_and_Patterns_of.99248.aspx

2. Cannabis Consumption Patterns Parallel the East-West Gradient in Canadian Neural Tube Defect Incidence – An Ecological Study
https://www.researchgate.net/publication/337911618_Cannabis_Consumption_Patterns_Explain_the_East-West_Gradient_in_Canadian_Neural_Tube_Defect_Incidence_An_Ecological_Study

Status:
Whilst a known link between prenatal cannabis exposure (PCE) and anencephaly exists, the relationship of PCE with neural tube defects (NTD’s) generally has not been defined. Published data from Canada Health and Statistics Canada was used to assess this relationship. Both cannabis use and NTDs were shown to follow an east-west and north-south gradient. Last year cannabis consumption was significantly associated (P<0.0001; Cannabis use: time interaction P<0.0001). These results were confirmed when estimates of termination for anomaly were used. Canada Health population data allowed the calculation of an NTD O.R.=1.27 (95%C.I. 1.19-1.37; P<10-11) for high risk provinces v. the remainder with an attributable fraction in exposed populations of 16.52% (95%C.I. 12.22-20.62). Data show a robust positive statistical association between cannabis consumption as both a qualitative and quantitative variable and NTDs on a background of declining NTD incidence. In the context of multiple mechanistic pathways these strong statistical findings implicate causal mechanisms.

82 References – click on this link to access.
https://www.researchgate.net/publication/337911618_Cannabis_Consumption_Patterns_Explain_the_East-West_Gradient_in_Canadian_Neural_Tube_Defect_Incidence_An_Ecological_Study

3. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study. Response to Lane
https://bmjopen.bmj.com/content/6/11/e011891.responses

Status:
We wish to thank Dr Lane for his interest in our study. We are pleased to see statistical input to the issues of cannabis medicine as we feel that sophisticated statistical methodologies have much to offer this field.

Most of the concerns raised are addressed in our very detailed report. As described our research question was whether, in our sizeable body of evidence (N=13,657 RAPWA studies), we could find evidence for the now well-described cannabis vasculopathy and what such implications might be. As this was the first study of its type to apply formal quantitative measures of vascular stiffness to these questions it was not clear at study outset if there would be any effect, much less an estimate of effect size. In the absence of this information power calculations would be mere guesswork. Nor indeed are they mandatory in an exploratory study of this type. Similarly the primary focus of our work was on whether cannabis exposure was an absolute cardiovascular risk factor in its own right, and how it compared to established risk factors. Hence Table 2 contains our main results. The role of Table 1 is to illustrate the bivariate (uncorrected) comparisons which can be made, show the various groups involved, and compare the matching of the groups. It is not intended to be a springboard for effect-size-power calculations which are of merely esoteric interest.
Calculations detailing the observed effect size are clearly described in our text being 11.84% and 8.35% age advance in males and females respectively.

Mixed-effects models are the canonical way to investigate longitudinal data given a usual random error structure 1. We agree with Lane that unusual error structures can affect significance conclusions. Diagnostic tests run on our models confirm that the residuals had the usual spheroidal error structure so that the application of mixed-effects models in the classical way is quite satisfactory. Another way to investigate this issue is that of incremental model building comparing models with and without cannabis exposure terms. If one considers regression equations from our data with cannabis use treated either as a categorical (RA/CA ~ Days_Post-Cannabis * BMI + * Cannabis_Category) or a continuous (RA/(CA*BMI) ~ Cigs*SP + * Cannabis_Use +Chol+DP+HDL+HR+CRH) variable one notes firstly that terms including cannabis use remain significant in final models (after model reduction) and secondly that models which include cannabis exposure are significantly better than ones without (Categorical: AIC = 1088.56 v. 1090.22, Log.Ratio = 19.62, P = 0.0204; Continuous: AIC = 412.33 v. 419.73, Log.Ratio = 9.37, P = 0.0022). Unfortunately formatting rules for BMJ Rapid Responses do not allow us to include a detailed table of regression results in each model in the present reply. We also note that AIC’s are little used in our report, and simply indicate the direction of the ANOVA results comparing models linear, quadratic and cubic in chronological age. They also appear routinely in the display of mixed-effects model results. Their use in such contexts is methodologically unremarkable. Control groups are also spelled out in fine detail in Table 1, in all our Figures and in the text.

We are aware that various algorithms for vascular age have been reported in the literature. The list proposed by Lane is correct but non-exhaustive. Such algorithms are generally derived from known cardiovascular risk factors. As clearly stated in our report the algorithm for vascular age we employed is derived from the proprietary software used. As such its details have not been publicized and indeed are commercially protected information.

We have however been assured by AtCor on many occasions that it includes measures of chronological age, sex, arterial stiffness and height (which is important as it dictates distance and thus speed parameters for the reflected and augmented central arterial pressure waves) and is very well validated and tested. AtCor recently advised that their algorithm is based on a very large series of studies done with arterial stiffness published in 2005 2. As such it has distinct advantages over algorithms which do not include indices of arterial stiffness. The AtCor website includes a very interesting, informative and educative animated loop which clearly illustrates the complex relationship between chronological and vascular age as a function of arterial stiffness and vascular tone 3

We are keen to see advanced statistical methods applied to such questions. We are becoming interested in geospatial and spacetime analyses and its application to the important questions of cannabis epidemiology 4. We find the very breadth of the organ systems impacted by cannabis to be quite remarkable with effects on the brain, cardiovasculature, liver, lungs, testes, ovaries, gastrointestinal, endocrine, reproductive and immune systems being well described and constituting most of the body’s major systems 5 6. Testicular and several pediatric cancers have also been described as being cannabis-associated 5. Such a multisystem generality of toxicity suggests to us that some basic cellular functions may be deleteriously affected – as implied by its well described mitochondriopathy 7, its heavy epigenetic footprint 8, accelerated aging as described in our present report 9 or some multi-way interaction between these and other processes. Given that the cannabis industry is presently entering a major commercialization growth phase, and given the multigenerational implications of mitochondriopathy-epigenotoxicity (by direct: substrate supply including ATP, NAD+ and acetate; and indirect: RNA transfer and malate-aspartate and glycerol-3-phosphate shuttle; pathways 10) further study and elucidation of these points is becoming an increasingly imperative international research priority.

Apropos of the recent Covid-19 pandemic emergency it is also worth noting that since cannabis is immunosuppressive, is known to be damaging to lungs and airways and often carries chemical, microbial and fungal contaminants cannabis use and cannabis vaping is also likely to have a deleterious effect on the coronavirus epidemic. Such data implies an untoward convergence of two public health epidemics. Appropriate controls on cannabis use imply improved public health management of SARS-CoV-2.

10 References – click on this link to access. https://bmjopen.bmj.com/content/6/11/e011891.responses

4. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.
https://www.researchgate.net/publication/334368364_Cannabis_Teratology_Explains_Current_Patterns_of_Coloradan_Congenital_Defects_The_Contribution_of_Increased_Cannabinoid_Exposure_to_Rising_Teratological_Trends/link/5d2d4d39a6fdcc2462e3097c/download

Status
Rising Δ9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure.

Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down’s syndrome, ventricular septal defect, and patent ductus arteriosus rose, and along with central nervous system, cardiovascular, genitourinary, respiratory, chromosomal, and musculoskeletal defects rose 5 to 37 times faster than the birth rate (3.3%) to generate an excess of 11 753 (22%) major anomalies. Cannabis was the only drug whose use grew from 2000 to 2014 while pain relievers, cocaine, alcohol, and tobacco did not. The correlation of cannabis use with major defects in 2014 (2019 dataset) was R = .77, P = .0011. Multiple cannabinoids were linked with summary measures of congenital anomalies and were robust to multivariate adjustment.

66 References – click on this link to access
https://www.researchgate.net/publication/334368364_Cannabis_Teratology_Explains_Current_Patterns_of_Coloradan_Congenital_Defects_The_Contribution_of_Increased_Cannabinoid_Exposure_to_Rising_Teratological_Trends/link/5d2d4d39a6fdcc2462e3097c/download

5. Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics 2018; 13: 1208-1221.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773386/pdf/kepi-14-11-1633868.pdf
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ABSTRACT Recent data from the Kollins lab (‘Cannabinoid exposure and altered DNA methylation in rat and human sperm’ Epigenetics 2018; 13: 1208–1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers. The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis.

Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required. 

206 References – click on this link to access

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773386/pdf/kepi-14-11-1633868.pdf

6. Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.
https://www.ncbi.nlm.nih.gov/pubmed/32187114

Status:
These results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down’s syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity. The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada’s northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate
further.

139 references – click on this link to access https://www.ncbi.nlm.nih.gov/pubmed/32187114

7. The Potential Association Between Prenatal Cannabis use and Congenital Anomalies
https://journals.lww.com/journaladdictionmedicine/Citation/9000/The_Potential_Association_Between_Prenatal.99243.aspx

Status:
Rates of prenatal cannabis use are likely to rise with legalization, increasing social tolerability, and promotion in social media. Cannabis consumption does not appear to be a benign activity, and there may be significant risk factors to the developing fetus when used in pregnancy. Even as epidemiological data continue to emerge, The American College of Obstetricians and Gynecologists and The Society of Obstetricians and Gynecologists of Canada recommend that women avoid the use of cannabis during pregnancy.14 Whether we will definitively establish the risk of prenatal cannabis use on congenital anomalies using epidemiological approaches remains unclear; however, combing data from ecological and patient-level approaches will be crucial. Patient engagement and increasing awareness of the health implications of cannabis are critical first steps to highlight the potential risks of cannabis use in pregnancy.

14. References – click on this link to access
https://journals.lww.com/journaladdictionmedicine/Citation/9000/The_Potential_Association_Between_Prenatal.99243.aspx

8. America Addresses Two Epidemics – Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study
Status: Embargoed until publication.

Question: Since cannabis is immunosuppressive and is frequently variously contaminated, is its use associated epidemiologically with coronavirus infection rates?

Findings: Geospatial analytical techniques were used to combine coronavirus incidence, drug and cannabinoid use, population, ethnicity, international flight and income data. Cannabis use and daily cannabis use were associated with coronavirus incidence on both bivariate regression and after multivariable spatial regression with high levels of statistical significance. Cannabis use quintiles and cannabis legal status were also highly significant.

Meaning: Significant geospatial statistical associations were shown between cannabis use and coronavirus infection rates consistent with mechanistic reports and environmental exposure concerns.

Extracts from Abstract:

Results. Significant associations of daily cannabis use quintile with CVIR were identified with the highest quintile having a prevalence ratio 5.11 (95%C.I. 4.90-5.33), an attributable fraction in the exposed (AFE) 80.45% (79.61-81.25%) and an attributable fraction in the population of 77.80% (76.88-78.68%) with Chi-squared-for-trend (14,782, df=4) significant at P<10-500. Similarly when cannabis legalization was considered decriminalization was associated with an elevated CVIR prevalence ratio 4.51 (95%C.I. 4.45-4.58), AFE 77.84% (77.50-78.17%) and Chi-squared-for-trend (56,679, df=2) significant at P<10-500. Monthly and daily use were linked with CVIR in bivariate geospatial regression models (P=0.0027, P=0.0059). In multivariable additive models number of flight origins and population density were significant. In interactive geospatial models adjusted for international travel, ethnicity, income, population, population density and drug use, terms including last month cannabis were significant from P=7.3×10-15, daily cannabis use from P=7.3×10-11 and last month cannabis was independently associated (P=0.0365).

Conclusions and Relevance. Data indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation. Recent cannabis use is independently predictive of CVIR in both bivariate and multivariable adjusted models and intensity of use is significant in several interactions. Cannabis thus joins tobacco as a SARS2-CoV-2 risk factor.

Summary and Conclusions

The above research clearly shows the links with substance use and Mental illness, Autism, Congenital anomalies and Paediatric cancer including testicular cancer with marijuana use and abuse. Drug Free Australia respectfully and urgently requests a Position Statement and proposed actions from your Department regarding this research and how it can be further promoted and supported within Australia. We look forward to your timely response.

You can find a list of list of Ngo’s and Medical Professional who written support for Drug Free Australia’s Response to the commercialization of Cannabis/Marijuana/CBD in Australia

https://drugfree.org.au/images/pdf-files/homepagepdf/DRReeceSupport2020_updated6May2020.pdf.

Yours sincerely
Major Brian Watters AO B.A.
President
Drug Free Australia
PO Box 379
Seaford, SA 516

Source: https://www.sciencedirect.com/science/article/abs/pii/S0165032719320919 May 2020

Source: 20-Reasons-to-Vote-NO-in-2020-SAM-VERSION-Cannabis.pdf (saynopetodope.org.nz) May 2020

In what is sure to be a controversial finding among cannabis users and proponents, a review of existing research published this week in The Lancet Psychiatry suggests that a single dose of THC may induce a variety of psychiatric symptoms associated with schizophrenia and other psychiatric disorders.

According to a news release issued by The Lancet on March 17:

A single dose of the main psychoactive component in cannabis, tetrahydrocannabinol (THC), can induce a range of psychiatric symptoms, according to results of a systematic review and meta-analysis of 15 studies including 331 people with no history of psychotic or other major psychiatric disorders, published in The Lancet Psychiatry journal.

The study was funded by the Medical Research Council and was conducted by researchers from Kings College London, South London and the Maudsley NHS Foundation Trust, Imperial College London, Leiden University Medical Hospital, Yale University School of Medicine, Connecticut Mental Health Center, and VA Connecticut Healthcare System.

The study also notes that these psychiatric symptoms are not associated with cannabidiol (CBD), one of the other major active compounds in cannabis. The authors reviewed four studies examining CBD’s effects on the development of the same psychiatric symptoms, and no significant differences were found between the effects of CBD and the effects of a placebo. “In studies that focused on whether CBD counters THC-induced symptoms, one study identified reduced symptoms, using a modest sample, but three larger studies failed to replicate this finding.”

The aforementioned news release quotes King’s College professor Oliver Howes as saying, “As the THC-to-CBD ratio of street cannabis continues to increase, it is important to clarify whether these compounds can cause psychotic symptoms. Our finding that THC can temporarily induce psychiatric symptoms in healthy volunteers highlights the risks associated with the use of THC-containing cannabis products. This potential risk should be considered in discussions between patients and medical practitioners thinking about using cannabis products with THC. This work will also inform regulators, public health initiatives, and policy makers considering the medical use of THC-containing cannabis products or their legalisation for recreational use.” 

There’s an important distinction to note here. Although the researchers found that a dose of THC—which they say is roughly equivalent to a single joint—can induce symptoms that mimic those of certain psychiatric disorders, THC does not in fact cause said disorders in users. 

This will come as little surprise to cannabis users, who are well aware from decades of anecdotal evidence that smoking a joint can make some people a little paranoid, but it has certainly never made anyone schizophrenic.

To put things in perspective, consider that in a commentary he wrote for the Straight last August, author and activist Dana Larsen noted that “every analysis of relative drug harms lists cannabis as one of the safest psychoactive substances there is.”

You can read the paper, which is title “Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis”, at the Lancet Psychiatry website.

Source:  https://www.straight.com/cannabis/1374471/review-studies-suggests-thc-cannabis-could-induce-psychotic-symptoms-healthy-people  19^th March 2020

Abstract

Keywords: Accelerated aging; Biological age; Biomarkers of aging; Cannabis and aging.

Source: Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study – PubMed (nih.gov) November 2016

A meta-analysis of all studies worldwide showing association between marijuana use and schizophrenia:

Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319–328.
http://dirwww.colorado.edu/alcohol/downloads/Cannabis_and_behavior.pdf

“There was an increased risk of any psychotic outcome in individuals who had ever used cannabis…with greater risk in people who used cannabis most frequently. There is now sufficient evidence to warn young people that using cannabis could increase their risk of
developing a psychotic illness later in life.”

The most recent study conducted in the United States (Columbia University, New York), showing a high risk (odds ratio, “OR”) for schizophrenia spectrum disorders, particularly in those who become cannabis-dependent:

Davis GP, Compton MT, Wang S, Levin FR, Blanco C. Association between cannabis use, psychosis, and schizotypal personality disorder: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Schizophr Res. 2013 Dec;151(1-3):197-202.
“There was a similar dose-response relationship between the extent of cannabis use and schizotypal personality disorder (OR=2.02 for lifetime cannabis use, 95% CI 1.69-2.42; OR=2.83 for lifetime cannabis abuse, 95% CI 2.33-2.43; OR=7.32 for lifetime cannabis dependence, 95% CI 5.51-9.72). Likelihood of individual schizotypal features increased significantly with increased extent of cannabis use in a dose-dependent manner.”

Studies that corrected for general genetic background effects and many non-cannabis environmental variables by comparing siblings. The risk ratios are somewhat lower than general population studies, because genetic predisposition is more or less controlled for:

McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh MR, Alati R, Williams GM, Bor W, Najman JM. Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults. Arch Gen Psychiatry. 2010; 67(5):440-7.
“Longer duration since first cannabis use was associated with multiple psychosis-related outcomes in young adults… the longer the duration since first cannabis use, the higher the risk of psychosis-related outcomes…
Compared with those who had never used cannabis, young adults who had 6 or more years since first use of cannabis (i.e., who commenced use when around 15 years or younger) were twice as likely to develop a nonaffective psychosis…
This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.”

Giordano GN, Ohlsson H, Sundquist K, Sundquist J, Kendler KS. The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study.
Psychol Med. 2014 Jul 3:1-8. [Epub ahead of print]
http://journals.cambridge.org/download.php?file=%2FPSM%2FS0033291714001524a.pdf&code=79f795824a92c8eead870197ef071dd8

“Allowing 7 years from initial CA registration to later diagnosis, the risk for schizophrenia in discordant full sibling pairs remained almost twofold….The results of this study therefore lend support to the etiologic hypothesis, that CA is one direct cause of later schizophrenia.”

Those diagnosed with schizophrenia who also use recreational drugs are much more likely to be violent, including those who use cannabis:

Fazel S, Långström N, Hjern A, Grann M, Lichtenstein P. Schizophrenia, substance abuse, and violent crime. JAMA. 2009 May 20;301(19):2016-23.
“The risk was mostly confined to patients with substance abuse comorbidity (of whom 27.6% committed an offense), yielding an increased risk of violent crime among such patients (adjusted OR, 4.4; 95% CI,3.9-5.0), whereas the risk increase was small in schizophrenia patients without substance abuse comorbidity (8.5% of whom had at least 1 violent offense; adjusted OR,1.2; 95% CI, 1.1-1.4; P<0.001 for interaction).”

Fazel S, Gulati G, Linsell L, Geddes JR, Grann M. Schizophrenia and violence: systematic review and meta-analysis. PLoS Med. 2009 Aug;6(8):e1000120. doi: 10.1371/journal.pmed.1000120. Epub 2009 Aug 11.
“The effect of comorbid substance abuse was marked with….. an OR of 8.9” (as compared to the general population)

Arseneault L, Moffitt TE, Caspi A, Taylor PJ, Silva PA. Mental disorders and violence in a total birth cohort: results from the Dunedin Study. Arch Gen Psychiatry. 2000;57(10):979-86.
“for having more than two of these disorders at once…..the OR (odds ratio for violence) was, …..for marijuana dependence plus schizophrenia spectrum disorder, 18.4”

Harris AW, Large MM, Redoblado-Hodge A, Nielssen O, Anderson J, Brennan J. Clinical and cognitive associations with aggression in the first episode of psychosis. Aust N Z J Psychiatry. 2010 Jan;44(1):85-93.
‘The use of cannabis with a frequency of more than fourfold in the previous month was the only factor that was found to be associated with serious aggression’

Self-report of psychotic symptoms by otherwise healthy users (12% to 15%):

Thomas H. A community survey of adverse effects of cannabis use. Drug Alcohol Depend. 1996 Nov;42(3):201-7.
“This survey estimates the frequency of various adverse effects of the use of the drug cannabis. A sample of 1000 New Zealanders aged 18-35 years were asked to complete a self-administered questionnaire on cannabis use and associated problems. The questionnaire was derived from criteria for the identification of cannabis abuse which are analagous to criteria commonly used to diagnose alcoholism. Of those who responded 38% admitted to having used cannabis. The most common physical or mental health problems, experienced by 22% of users were acute anxiety or panic attacks following cannabis use. Fifteen percent reported psychotic symptoms following use.”

Smith MJ, Thirthalli J, Abdallah AB, Murray RM, Cottler LB. Prevalence of psychotic symptoms in substance users: a comparison across substances. Compr Psychiatry. 2009 May-Jun;50(3):245-50. doi: 10.1016/j.comppsych.2008.07.009. Epub 2008 Sep 23.
“Among all users of substances without a diagnosis of abuse or dependence, cannabis users reported the highest prevalence of psychotic symptoms (12.4%).”

Barkus EJ, Stirling J, Hopkins RS, Lewis S.. Cannabis-induced psychosis-like experiences are associated with high schizotypy Psychopathology 2006;39(4):175-8.
“In the sample who reported ever using cannabis (72%) the means for the subscales from the CEQ were as follows: ……Psychotic-Like Experiences (12.98%).”

Rates of psychotic symptoms in those with cannabis dependence as compared to non-dependent users and nonusers:

Fergusson DM, Horwood LJ, Swain-Campbell NR. Cannabis dependence and psychotic symptoms in young people. Psychol Med. 2003 Jan;33(1):15-21.
“Young people meeting DSM-IV criteria for cannabis dependence had elevated rates of psychotic symptoms at ages 18 (rate ratio = 3.7; 95% CI 2.8-5.0; P < 0.0001) and 21 (rate ratio = 2.3; 95% CI 1.7-3.2; P < 0.0001).”

Smith MJ, Thirthalli J, Abdallah AB, Murray RM, Cottler LB. Prevalence of psychotic symptoms in substance users: a comparison across substances. Compr Psychiatry. 2009 May-Jun;50(3):245-50. doi: 10.1016/j.comppsych.2008.07.009. Epub 2008 Sep 23.
“more than half of the respondents who were dependent on cocaine (80%), cannabis (63.5%), amphetamines (56.1%), and opiates (53.1%) reported psychotic symptoms. Among all users of substances without a diagnosis of abuse or dependence, cannabis users reported the highest prevalence of psychotic symptoms (12.4%)……. There was also a marked increase in the risk for psychotic symptoms when dependence became moderate or severe for cannabis (OR=25.1, OR=26.8; respectively).”

Studies on the psychotomimetic properties of THC administered to healthy individuals in the clinic:

D’Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, Braley G, Gueorguieva R, Krystal JH. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 2004 Aug;29(8):1558-72.
“∆-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception;(3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that D-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses.”

Morrison PD, Nottage J, Stone JM, Bhattacharyya S, Tunstall N, Brenneisen R, Holt D, Wilson D, Sumich A, McGuire P, Murray RM, Kapur S, Ffytche DH. Disruption of frontal θ coherence by ∆9-tetrahydrocannabinol is associated with positive psychotic symptoms. Neuropsychopharmacology. 2011;;36(4):827-36.
“Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001)…… The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.”

Bhattacharyya S, Crippa JA, Allen P, Martin-Santos R, Borgwardt S, Fusar-Poli P, Rubia K, Kambeitz J, O’Carroll C, Seal ML, Giampietro V, Brammer M, Zuardi AW, Atakan Z, McGuire PK. Induction of psychosis by ∆9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch Gen Psychiatry. 2012 Jan;69(1):27-36. doi: 10.1001/archgenpsychiatry.2011.161.
“Pairwise comparisons revealed that 9-THC significantly increased the severity of psychotic symptoms compared with placebo (P<.001) and CBD (P<.001).”,

Freeman D, Dunn G, Murray RM, Evans N, Lister R, Antley A, Slater M, Godlewska B, Cornish R, Williams J, Di Simplicio M, Igoumenou A, Brenneisen R, Tunbridge EM, Harrison PJ, Harmer CJ, Cowen P, Morrison PD. How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia. Schizophr Bull. 2014 Jul 15. pii: sbu098. [Epub ahead of print]
“THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity.”

For data on dose-response (a very large study by Zammit et al., and another by van Os et al.) and the greater risk for psychosis posed by high strength marijuana (DiForti et al.):

Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G, 2002, Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 2002 Nov 23;325(7374):1199. http://www.bmj.com/content/325/7374/1199.full.pdf
“We found a dose dependent relation between frequency of cannabis use and risk of schizophrenia, with an adjusted odds ratio for linear trend across the categories of frequency of cannabis use used in this study of 1.2 (1.1 to 1.4, P < 0.001). The adjusted odds ratio for subjects with a history of heaviest use of cannabis ( > 50 occasions) was 3.1 (1.7 to 5.5)………………Cannabis use is associated with an increased risk of
developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration.”

van Os J, Bak M, Hanssen M, Bijl RV, de Graaf R, Verdoux H. Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol. 2002 Aug 15;156(4):319-27.
“…..further evidence supporting the hypothesis of a causal relation is demonstrated by the existence of a dose-response relation.. between cumulative exposure to cannabis use and the psychosis outcome……. About 80 percent of the psychosis outcome associated with exposure to both cannabis and an established vulnerability to psychosis was attributable to the synergistic action of these two factors. This finding indicates that, of the subjects exposed to both a vulnerability to psychosis and cannabis use, approximately 80 percent had the psychosis outcome because of the combined action of the two risk factors and only about 20 percent because of the action of either factor alone.”

DiForti M, Morgan C, Dazzan P, Pariante C, Mondelli V, Marques TR, Handley R, Luzi S, Russo M, Paparelli A, Butt A, Stilo SA, Wiffen B, Powell J, Murray RM. High-potency cannabis and the risk of psychosis. Br J Psychiatry. 2009,195(6):488-91.
“78% (n = 125) of the cases group preferentially used sinsemilla (skunk) compared with only 31% (n = 41) of the control group (unadjusted OR= 8.1, 95% CI 4.6–13.5). This association was only slightly attenuated after controlling for potential confounders (adjusted OR= 6.8, 95% CI 2.6–25.4)………. Our most striking finding is that patients with a first episode of psychosis preferentially used high-potency cannabis preparations of the sinsemilla (skunk) variety…… our results suggest that the potency and frequency of cannabis use may interact in further increasing the risk of psychosis.”

DiForti M, Marconi A, Carra E, Fraietta S, Trotta A, Bonomo M, Bianconi F, Gardner-Sood P, O’Connor J, Russo M, Stilo SA, Marques TR, Mondelli V, Dazzan P, Pariante C, David AS, Gaughran F, Atakan Z, Iyegbe C, Powell J, Morgan C, Lynskey M, Murray RM. Proportion of
patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. Lancet Psychiatry, online February 18, 2015, http://dx.doi.org/10.1016/S2215-0366(14)00117-5.
“In the present larger sample analysis, we replicated our previous report and showed that the highest probability to suffer a psychotic disorder is in those who are daily users of high potency cannabis. Indeed, skunk use appears to contribute to 24% of cases of first episode psychosis in south London. Our findings show the importance of raising awareness among young people of the risks associated with the use of high-potency cannabis. The need for such public education is emphasised by the worldwide trend of liberalisation of the legal constraints on cannabis and the fact that high potency varieties are becoming much more widely available.”

For data on percent of those with marijuana-induced psychosis who go on to receive a diagnosis of a schizophrenia spectrum disorder:

Arendt M, Mortensen PB, Rosenberg R, Pedersen CB, Waltoft BL. Familial predisposition for psychiatric disorder: comparison of subjects treated for cannabis-induced psychosis and schizophrenia. Arch Gen Psychiatry. 2008;65(11):1269-74. http://archpsyc.ama-assn.org/cgi/reprint/65/11/1269
“Approximately half of the subjects who received treatment of a cannabis induced psychosis developed a schizophrenia spectrum disorder within 9 years after treatment…… The risk of schizophrenia after a cannabis-induced psychosis is independent of familial predisposition……. cannabis-induced psychosis may not be a valid diagnosis but an early marker of schizophrenia……. Psychotic symptoms after cannabis
use should be taken extremely seriously.”

Niemi-Pynttäri JA, Sund R, Putkonen H, Vorma H, Wahlbeck K, Pirkola SP. Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases. J Clin Psychiatry. 2013 74(1):e94-9.
“Eight-year cumulative risk to receive a schizophrenia spectrum diagnosis was 46% for persons with a diagnosis of cannabis-induced psychosis ….. chances for amphetamine-, hallucinogen-, opioid-, sedative- and alcohol-induced (schizophrenia spectrum diagnoses) were 30%, 24%, 21%, and 5% respectively.”

For cause and effect (which comes first: psychosis or marijuana use):
Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE, 2002, Cannabis use in
adolescence and risk for adult psychosis: longitudinal prospective study.BMJ. 2002 Nov 23;325(7374):1212-3.
“Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). Thirdly, risk was specific to cannabis use, as opposed to use of other drugs….”

Henquet C, Krabbendam L, Spauwen J, et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ. 2005;330:11–15. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539839/pdf/bmj33000011.pdf
“Exposure to cannabis during adolescence and young adulthood increases the risk of psychotic symptoms later in life. Cannabis use at baseline increased the cumulative incidence of psychotic symptoms at follow up four years later…but has a much stronger effect in those with evidence of predisposition for psychosis……….Predisposition for psychosis at baseline did not significantly predict cannabis use four years later..”

and also:

Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study.BMJ. 2011 Mar 1;342: d738 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047001/pdf/bmj.d738.pdf
“In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline, incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 (adjusted odds ratio 1.9, 95% confidence interval 1.1 to 3.1; P=0.021)…………There was no evidence for self medication effects, as psychotic experiences at T2 did not predict incident cannabis use between T2 and T3 (0.8, 0.6 to 1.2; P=0.3).”

For data on those who quit using when psychotic symptoms develop (further evidence against self-medication):

Fergusson DM, Horwood LJ, Ridder EM. Tests of causal linkages between cannabis use and psychotic symptoms. Addiction. 2005;100(3):354-66.

For degree of risk relative to other drugs:

Niemi-Pynttäri JA, Sund R, Putkonen H, Vorma H, Wahlbeck K, Pirkola SP. Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases. J Clin Psychiatry. 2013 74(1):e94-9.
“Eight-year cumulative risk to receive a schizophrenia spectrum diagnosis was 46% for persons with a diagnosis of cannabis-induced psychosis ….. chances for amphetamine-, hallucinogen-, opioid-, sedative- and alcohol-induced (schizophrenia spectrum diagnoses) were 30%, 24%, 21%, and 5% respectively.”

Smith MJ, Thirthalli J, Abdallah AB, Murray RM, Cottler LB. Prevalence of psychotic symptoms in substance users: a comparison across substances. Compr Psychiatry. 2009 May-Jun;50(3):245-50. doi: 10.1016/j.comppsych.2008.07.009. Epub 2008 Sep 23.
“more than half of the respondents who were dependent on cocaine (80%), cannabis (63.5%), amphetamines (56.1%), and opiates (53.1%) reported psychotic symptoms. Among all users of substances without a diagnosis of abuse or dependence, cannabis users reported the highest prevalence of psychotic symptoms (12.4%)……. There was also a marked increase in the risk for psychotic symptoms when dependence became moderate or severe for cannabis (OR=25.1, OR=26.8; respectively).”

Another angle on the potential confound of self-medication: genetic predisposition for schizophrenia does not predict cannabis use:

Veling W, Mackenbach JP, van Os J, Hoek HW. Cannabis use and genetic predisposition for schizophrenia: a case-control study. Psychol Med. 2008 Sep;38(9):1251-6. Epub 2008 May 19.
“BACKGROUND: Cannabis use may be a risk factor for schizophrenia. RESULTS: Cannabis use predicted schizophrenia [adjusted odds ratio (OR) cases compared to general hospital controls 7.8, 95% confidence interval (CI) 2.7-22.6; adjusted OR cases compared to siblings 15.9 (95% CI 1.5-167.1)], but genetic predisposition for schizophrenia did not predict cannabis use [adjusted OR intermediate predisposition
compared to lowest predisposition 1.2 (95% CI 0.4-3.8)].”

For data on potential benefits of cessation:

González-Pinto A, Alberich S, Barbeito S, Gutierrez M, Vega P, Ibáñez B, Haidar MK, Vieta E, Arango C. Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use. Schizophr Bull. 2011 May;37(3):631-9. Epub 2009 Nov 13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080669/pdf/sbp126.pdf
“OBJECTIVE: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up….. CONCLUSION: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.”

Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study.BMJ. 2011 Mar 1;342: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047001/pdf/bmj.d738.pdf
“The finding that longer exposure to cannabis was associated with greater risk for persistence of psychotic experiences is in line with an earlier study showing that continued cannabis use over time increases the risk for psychosis in a dose-response fashion. This is also in agreement with the hypothesis that a process of sensitisation might underlie emergence and persistence of psychotic experiences as an indicator of liability to psychotic disorder.”

For data on marijuana use resulting in an earlier age of onset of schizophrenia (suggestive of causality), see Dragt et al. and a meta-analysis (see Large et al.,); also: a very extensive (676 schizophrena patients) and therefore more statistically powered analysis (see DeHert paper); two papers showing that the age-of-onset effect may be specific to those without a family history (see Scherr et al. and Leeson et al., papers); two studies that evaluate the age of onset specific to gender (Veen et al. and Compton et al. ) which is important because comparing across genders can be confounded by the greater tendency of males to engage in risky behavior (the conclusions are not the same in terms of gender; the gender distribution was slightly better in the Veen et al. study) and finally, two papers of relevance to specificity of age of onset effect to cannabis, a meta-analysis of published studies on age of onset that shows another drug of abuse (tobacco) is not associated with
a decreased age of onset (Myles et al.) and a study showing that ecstasy, LSD, stimulants, or sedatives did not have an effect to lower age of onset whereas cannabis use did (Barnes et al.) :

Large M, Sharma S, Compton MT, Slade T, Nielssen O. Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-analysis. Arch Gen Psychiatry. 2011 68(6):555-61. http://www.ncbi.nlm.nih.gov/pubmed/21300939
“The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.”

Dragt S, Nieman DH, Schultze-Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RK, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH; on behalf of the EPOS group.Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Acta Psychiatr Scand. 2011 Aug 29. doi: 10.1111/j.1600-0447.2011.01763.x. [Epub ahead of print]
“Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Objective: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis
use and early and high-risk symptoms in subjects at clinical high risk for psychosis. Results: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < r(s) < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants. Conclusion: Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals.”

De Hert M, Wampers M, Jendricko T, Franic T, Vidovic D, De Vriendt N, Sweers K, Peuskens J, van Winkel R.Effects of cannabis use on age at onset in schizophrenia and bipolar disorder. Schizophr Res. 2011 Mar;126(1-3):270-6.

“BACKGROUND: Cannabis use may decrease age at onset in both schizophrenia and bipolar disorder, given the evidence for substantial phenotypic and genetic overlap between both disorders….RESULTS:… Both cannabis use and a schizophrenia diagnosis predicted earlier age at onset. There was a significant interaction between cannabis use and diagnosis, cannabis having a greater effect in bipolar patients….DISCUSSION:…. Our results suggest that cannabis use is associated with a reduction in age at onset in both schizophrenic and bipolar patients. This reduction seems more pronounced in the bipolar group than in the schizophrenia group: the use of cannabis reduced age at onset by on average 8.9 years in the bipolar group, as compared to an average predicted reduction of 1.5 years in the schizophrenia group.”

Scherr M, Hamann M, Schwerthöffer D, Froböse T, Vukovich R, Pit schel-Walz G, Bäuml J.. Environmental risk factors and their impact on the age of onset of schizophrenia: Comparing familial to non-familial schizophrenia. Nord J Psychiatry. 2011 Aug 31. [Epub ahead of print]
“Background and aims: Several risk factors for schizophrenia have yet been identified. The aim of our study was to investigate how certain childhood and adolescent risk factors predict the age of onset of psychosis in patients with and without a familial component (i.e. a relative with schizophrenia or schizoaffective disorder). Results: Birth complications and cannabis abuse are predictors for an earlier onset of schizophrenia in patients with non-familial schizophrenia. No environmental risk factors for an earlier age of onset in familial schizophrenia have been identified.”

Leeson VC, Harrison I, Ron MA, Barnes TR, Joyce EM. The Effect of Cannabis Use and Cognitive Reserve on Age at Onset and Psychosis Outcomes in First-Episode Schizophrenia. Schizophr Bull. 2011 Mar 9. [Epub ahead of print] http://schizophreniabulletin.oxfordjournals.org/content/early/2011/03/09/schbul.sbq153.full.pdf+html
“Objective: Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use……Conclusions: Cannabis use brings forward the onset of psychosis in people who otherwise have good prognostic features indicating that an early age at onset can be due to a toxic action of cannabis rather than an intrinsically more severe illness. Many patients abstain over time, but in those who persist, psychosis is more difficult to treat.”

Veen ND, Selten JP, van der Tweel I, Feller WG, Hoek HW, Kahn RS. Cannabis use and age at onset of schizophrenia. Am J Psychiatry. 2004 Mar;161(3):501-6. http://ajp.psychiatryonline.org/cgi/reprint/161/3/501
“The results indicate a strong association between use of cannabis and earlier age at first psychotic episode in male schizophrenia patients.”

Compton MT, Kelley ME, Ramsay CE, Pringle M, Goulding SM, Esterberg ML, Stewart T, Walker EF. Association of pre-onset cannabis, alcohol, and tobacco use with age at onset of prodrome and age at onset of psychosis in first-episode patients. Am J Psychiatry. 2009 Nov;166(11):1251-7. Epub 2009 Oct 1. http://ajp.psychiatryonlie.org/cgi/reprint/166/11/1251
“Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of (editor’s note: “timing of”) onset, analysis of change in frequency of use prior to
onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males.”

Myles N, Newall H, Compton MT, Curtis J, Nielssen O, Large M. The age at onset of psychosis and tobacco use: a systematic meta-analysis. Soc Psychiatry Psychiatr Epidemiol. 2011 Sep 8. [Epub ahead of print]
“Unlike cannabis use, tobacco use is not associated with an earlier onset of psychosis.”

Barnes TR, Mutsatsa SH, Hutton SB, Watt HC, Joyce EM. Comorbid substance use and age at onset of schizophrenia. Br J Psychiatry. 2006 Mar;188:237-42. http://bjp.rcpsych.org/content/188/3/237.full.pdf+html
“Alcohol misuse and any substance use (other than cannabis use) were not significant in relation to age at onset….. those patients in the sample who reported that they had used cannabis had an earlier age at onset of psychosis than other patients who did not report cannabis use but who shared the same profile with regard to the other variables (e.g. comparing men who reported alcohol misuse and use of both cannabis and other drugs with men who had the same characteristics apart from the fact that they had not used cannabis).”

Data from other cultures

Sarkar J, Murthy P, Singh SP. Psychiatric morbidity of cannabis abuse. Indian J Psychiatry. 2003 Jul;45(3):182-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952166/pdf/IJPsy-45-182.pdf
“The paper evaluates the hypothesis that cannabis abuse is associated with a broad range of psychiatric disorders in India, an area with relatively high prevalence of cannabis use. Retrospective case-note review of all cases with cannabis related diagnosis over a 11 -year period, for subjects presenting to a tertiary psychiatric hospital in southern India was carried out. Information pertaining to sociodemographic, personal, social, substance-use related, psychiatric and treatment histories, was gathered. Standardized diagnoses were made according to Diagnostic Criteria for Research of the World Health Organization, on the basis of information available.Cannabis abuse is associated with
widespread psychiatric morbidity that spans the major categories of mental disorders under the ICD-10 system, although proportion of patients with psychotic disorders far outweighed those with non-psychotic disorders. Whilst paranoid psychoses were more prevalent, a significant number of patients with affective psychoses, particularly mania, was also noted.”

Rodrigo C, Welgama S, Gunawardana A, Maithripala C, Jayananda G, Rajapakse S. A retrospective analysis of cannabis use in a cohort of mentally ill patients in Sri Lanka and its implications on policy development. Subst Abuse Treat Prev Policy. 2010 Jul 8;5:16. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910013/pdf/1747-597X-5-16.pdf
”BACKGROUND: Several epidemiological studies have shown that cannabis; the most widely used illegal drug in the world, is associated with schizophrenia spectrum disorders (SSD)……. CONCLUSIONS: Self reported LTC (editor’s note: life time cannabis) use was strongly associated with being diagnosed with SSD (editor’s note: schizophrenia spectrum disorders”.

Population study showing change in incidence rate in young when drug laws are eased

Ajdacic-Gross V, Lauber C, Warnke I, Haker H, Murray RM, Rössler W. Changing incidence of psychotic disorders among the young in Zurich. Schizophr Res. 2007 Sep;95(1-3):9-18. Epub 2007 Jul 16.
“There is controversy over whether the incidence rates of schizophrenia and psychotic disorders have changed in recent decades. To detect deviations from trends in incidence, we analysed admission data of patients with an ICD-8/9/10 diagnosis of psychotic disorders in the Canton Zurich / Switzerland, for the period 1977-2005. The data was derived from the central psychiatric register of the Canton Zurich. Ex-post forecasting with ARIMA (Autoregressive Integrated Moving Average) models was used to assess departures from existing trends. In addition, age-period-cohort analysis was applied to determine hidden birth cohort effects. First admission rates of patients with psychotic
disorders were constant in men and showed a downward trend in women. However, the rates in the youngest age groups showed a strong increase in the second half of the 1990’s. The trend reversal among the youngest age groups coincides with the increased
use of cannabis among young Swiss in the 1990’s.”

Estimates of how many men aged 20-40 would have to avoid regular marijuana use for one year in order to prevent one case of schizophrenia in that same year (but for number relevant to a 20 year avoidance of schizophrenia by avoiding regular marijuana use during
20 years, divide by 20):

Hickman M, Vickerman P, Macleod J, Lewis G, Zammit S, Kirkbride J, Jones P. If cannabis caused schizophrenia–how many cannabis users may need to be prevented in order to prevent one case of schizophrenia? England and Wales calculations. Addiction. 2009;104(11):1856-61.

“In men the annual mean NNP (number needed to prevent) for heavy cannabis and schizophrenia ranged from 2800 [90% confidence interval (CI) 2018–4530] in those aged 20–24 years to 4700 (90% CI 3114–8416) in those aged 35–39”.

Key studies interpreted to diminish the connection between marijuana and schizophrenia:

Proal AC, Fleming J, Galvez-Buccollini JA, Delisi LE. A controlled family study of cannabis users with and without psychosis. Schizophr Res. 2014 Jan;152(1):283-8.
“The results of the current study, both when analyzed using morbid risk and family frequency calculations, suggest that having an increased familial risk for schizophrenia is the underlying basis for schizophrenia in these samples and not the cannabis use. While cannabismay have an effect on theage of onset of schizophrenia it is unlikely to be the cause of illness.”

Rebuttal: Miller CL. Caution urged in interpreting a negative study of cannabis use and schizophrenia. Schizophr Res. 2014 Apr;154(1-3):119-20.
“The morbid risk reported for the relatives of the non-cannabis-using patients (Sample 3) was actually 1.4-fold higher than the cannabis using patients (Sample 4), but the study did not have enough power to statistically confirm or refute a less than 2-fold difference. An increase in sample size would be required to do so, and if the observed difference were to be confirmed, it would explain not only why the Sample 4 data fits poorly with a multigene/small environmental impact model but also would give weight to the premise that cannabis use significantly contributes to the development of this disease.”

Power RA, Verweij KJ, Zuhair M, Montgomery GW, Henders AK, Heath AC, Madden PA, Medland SE, Wray NR, Martin NG. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry. 2014 Jun 24. doi: 10.1038/mp.2014.51. [Epub ahead of print] http://emilkirkegaard.dk/en/wp-content/uploads/Genetic%20predisposition%20to%20schizophrenia%20associated%20with%20increased%20use%20of%20cannabis.pdf
“Our results show that to some extent the association between cannabis and schizophrenia is due to a shared genetic aetiology across common variants. They suggest that individuals with an increased genetic predisposition to schizophrenia are
both more likely to use cannabis and to use it in greater quantities.”

Rebuttal: Had this paper been titled “The causal genes for schizophrenia have been discovered” it would never have been published. In the absence of a consistent finding of genes of major effect size for schizophrenia, this study of inconsistently associated genes of low effect size is meaningless.

Buchy L, Perkins D, Woods SW, Liu L, Addington J. Impact of substance use on conversion to psychosis in youth at clinical high risk of psychosis. Schizophrenia Res 156 (2-3): 277–280.
“Results revealed that low use of alcohol, but neither cannabis use nor tobacco use at baseline, contributed to the prediction of psychosis in the CHR sample”.
Rebuttal: The study was small in size and the age range of their subjects at study onset was large (12 to 31) which included both subjects that had not reached the peak age of risk for schizophrenia even by the end of the study as well as subjects who were well past the peak age of onset of schizophrenia. The fact that the study screened out psychotic individuals was problematic for the latter group, in that those who were most vulnerable to the psychosis inducing effects of cannabis would already have converted to psychosis by that age.

Overview of Key Public Health Issues Regarding the Mental Health Effects of Marijuana

For the monetary cost of schizophrenia to the U.S. annually ($63 billion in 2002 dollars):

Wu EQ, Birnbaum HG, Shi L, Ball DE, Kessler RC, Moulis M, Aggarwal J. The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry. 2005 Sep;66(9):1122-9.

For the trends in adolescent drug, alcohol and cigarette use, showing an upward tick in marijuana use as medical marijuana has become more prevalent, and that the mind-altering drug legal for adults (alcohol) is still more commonly used by teens than is marijuana:

Johnston, L. D., O’Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (2012). Monitoring the Future national results on adolescent drug use: Overview of key findings, 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan.

For a summary of Sweden’s drug law experience:
Hallam C., 2010, Briefing paper 20, The Beckley Foundation: What Can We Learn from Sweden’s Drug Policy Experience? www.beckleyfoundation.org/pdf/BriefingPaper_20.pdf
“in the case of Sweden, the clear association between a restrictive drug policy and low levels of drug use is striking. In his foreword to the article on Sweden’s Successful Drug Policy, Antonio Maria Costa is frank enough to confess that, “It is my firm belief that the generally positive situation of Sweden is a result of the policy that has been applied to address the problem”.

For data showing the relationship between drug enforcement policies in Europe and drug use, such that Sweden has a zero tolerance policy on drugs and has one of the lowest rates of “last month use” in Europe (1%), 4-fold lower than the Netherlands and 7-fold lower than Spain and Italy, two countries that have liberalized their enforcement policies so that marijuana possession carries no substantive penalty.

European Monitoring Centre for Drugs and Addiction, 2012 Annual report
http://www.emcdda.europa.eu/attachements.cfm/att_190854_EN_TDAC12001ENC_.pdf

Source: Microsoft Word – 2015- Summary of literature on marijuana and psychosis.doc (momsstrong.org) January 2016

(-)-Trans-Δ9-tetrahydrocannabinol (Δ9-THC) is the main compound responsible for the intoxicant activity of Cannabis sativa L. The length of the side alkyl chain influences the biological activity of this cannabinoid. In particular, synthetic analogues of Δ9-THC with a longer side chain have shown cannabimimetic properties far higher than Δ9-THC itself. In the attempt to define the phytocannabinoids profile that characterizes a medicinal cannabis variety, a new phytocannabinoid with the same structure of Δ9-THC but with a seven-term alkyl side chain was identified.

The natural compound was isolated and fully characterized and its stereochemical configuration was assigned by match with the same compound obtained by a stereoselective synthesis. This new phytocannabinoid has been called (-)-trans-Δ9-tetrahydrocannabiphorol (Δ9-THCP). Along with Δ9-THCP, the corresponding cannabidiol (CBD) homolog with seven-term side alkyl chain (CBDP) was also isolated and unambiguously identified by match with its synthetic counterpart. The binding activity of Δ9-THCP against human CB1 receptor in vitro (Ki=1.2nM) resulted similar to that of CP55940 (Ki=0.9nM), a potent full CB1 agonist. In the cannabinoid tetrad pharmacological test, Δ9-THCP induced hypomotility, analgesia, catalepsy and decreased rectal temperature indicating a THC-like cannabimimetic activity.
The presence of this new phytocannabinoid could account for the pharmacological properties of some cannabis varieties difficult to explain by the presence of the sole Δ9-THC.

Cannabis sativa has always been a controversial plant as it can be considered as a lifesaver for several pathologies including glaucoma and epilepsy, an invaluable source of nutrients, an environmentally friendly raw material for manufacturing and textiles, but it is also the most widely spread illicit drug in the world, especially among young adults
.
Its peculiarity is its ability to produce a class of organic molecules called phytocannabinoids, which derive from an enzymatic reaction between a resorcinol and an isoprenoid group. The modularity of these two parts is the key for the extreme variability of the resulting product that has led to almost 150 different known phytocannabinoids. The precursors for the most commonly naturally occurring phytocannabinoids are olivetolic acid and geranyl pyrophosphate, which take part to a condensation reaction leading to the formation of cannabigerolic acid (CBGA). CBGA can be then converted into either tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA) or cannabichromenic acid (CBCA) by the action of a specific cyclase enzyme. All phytocannabinoids are biosynthesized in the carboxylated form, which can be converted into the corresponding decarboxylated (or neutral) form by heat.

The best known neutral cannabinoids are undoubtedly Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the former being responsible for the intoxicant properties of the cannabis plant, and the latter being active as antioxidant, anti-inflammatory, anti-convulsant, but also as antagonist of THC negative effects.
All these cannabinoids are characterized by the presence of an alkyl side chain on the resorcinol moiety made of five carbon atoms. However, other phytocannabinoids with a different number of carbon atoms on the side chain are known and they have been called varinoids (with three carbon atoms), such as cannabidivarin (CBDV) and Δ9-tetrahydrocannabivarin (Δ9 -THCV), and orcinoids (with one carbon atom), such as cannabidiorcol (CBD-C1) and tetrahydrocannabiorcol (THC-C1)7. Both series are biosynthesized in the plant as the specific ketide synthases have been identified.
Our research group has recently reported the presence of a butyl phytocannabinoid series with a four-term alkyl chain, in particular cannabidibutol (CBDB) and Δ9-tetrahydrocannabutol (Δ9-THCB), in CBD samples derived from hemp and in a medicinal cannabis variety. Since no evidence has been provided for the presence of plant enzymes responsible for the biosynthesis of these butyl phytocannabinoids, it has been suggested that they might derive from microbial ω-oxidation and decarboxylation of their corresponding five-term homolog.
The length of the alkyl side chain has indeed proved to be the key parameter, the pharmacophore, for the biological activity exerted by Δ9-THC on the human cannabinoid receptor CB1 as evidenced by structure-activity relationship (SAR) studies collected by Bow and Rimondi. In particular, a minimum of three carbons is necessary to bind the receptor, then the highest activity has been registered with an eight-carbon side chain to finally decrease with a higher number of carbon atoms. Δ8-THC homologs with more than five carbon atoms on the side chain have been synthetically produced and tested in order to have molecules several times more potent than Δ9-THC.
To the best of our knowledge, a phytocannabinoid with a linear alkyl side chain containing more than five carbon atoms has never been reported as naturally occurring. However, our research group disclosed for the first time the presence of seven-term homologs of CBD and Δ9-THC in a medicinal cannabis variety, the Italian FM2, provided by the Military Chemical Pharmaceutical Institute in Florence.

The two new phytocannabinoids were isolated and fully characterized and their absolute configuration was confirmed by a stereoselective synthesis. According to the International Non-proprietary Name (INN), we suggested for these CBD and THC analogues the name “cannabidiphorol” (CBDP) and “tetrahydrocannabiphorol” (THCP), respectively. The suffix “-phorol” comes from “sphaerophorol”, common name for 5-heptyl-benzen-1,3-diol, which constitutes the resorcinol moiety of these two new phytocannabinoids.
A number of clinical trials and a growing body of literature provide real evidence of the pharmacological potential of cannabis and cannabinoids on a wide range of disorders from sleep to anxiety, multiple sclerosis, autism and neuropathic pain20–23. In particular, being the most potent psychotropic cannabinoid, Δ9-THC is the main focus of such studies.

In light of the above and of the results of the SAR studies, we expected that THCP is endowed of an even higher binding affinity for CB1 receptor and a greater cannabimimetic activity than THC itself. In order to investigate these pharmacological aspects of THCP, its binding affinity for CB1 receptor was tested by a radioligand in vitro assay and its cannabimimetic activity was assessed by the tetrad behavioral tests
in mice.
Results
Identifcation of cannabidiphorol (CBDP) and Δ9-tetrahydrocannabiphorol (Δ9-THCP) by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS).

The FM2 ethanolic extract was analyzed by an analytical method recently developed for the cannabinoid profiling of this medicinal cannabis variety. As the native extract contains mainly the carboxylated forms of phytocannabinoids as a consequence of a cold extraction25, part of the plant material was heated to achieve decarboxylation where the predominant forms are neutral phytocannabinoids.

The advanced analytical platform of ultra-high performance liquid chromatography coupled to high resolution Orbitrap mass spectrometry was employed to analyze the FM2 extracts and study the fragmentation spectra of the analytes under investigation. The precursor ions of the neutral derivatives cannabidiphorol (CBDP) and Δ9-tetrahydrocannabiphorol (Δ9-THCP), 341.2486 for the [M-H]− and 343.2632 for the [M+H]+, showed an elution time of 19.4 min for CBDP and 21.3 min for Δ9-THCP (Fig. 1a).
Their identification was confirmed by the injection of a mixture (5 ng/mL) of the two chemically synthesized CBDP and Δ9-THCP (Fig. 1b) as it will be described later. As for their carboxylated counterpart, the precursor ions of the neutral forms CBDP and Δ9-THCP break in the same way in ESI+mode, but they show a different fragmentation pattern in ESI− mode. Whilst Δ9-THCP shows only the precursor ion [M-H]− (Fig. 1d), CBDP molecule generates the fragments at m/z 273.1858 corresponding to a retro Diels-Alder reaction, and 207.1381
corresponding to the resorcinol moiety after the break of the bond with the terpenoid group (Fig. 1c). It is noteworthy that for both molecules, CBDP and Δ9-THCP, each fragment in both ionization modes differ exactly by an ethylene unit (CH2)2 from the corresponding five-termed homologs CBD and THC.

Moreover, the longer elution time corroborates the hypothesis of the seven-termed phytocannabinoids considering the higher lipophilicity of the latter.

Source: https://www.nature.com/articles/s41598-019-56785-1 December 2019

Alex Azar
Secretary of Health and Human Services
US Department of Health and Human Services
200 Independence Avenue SW
Washington D.C, 20201
November 5, 2019

Dear Secretary Azar:
This letter is to bring to your attention a study underway at the University of Washington referred to as the “Moms and Marijuana Study” and granted under the title: “Olfactory Activation and Brain Development in Infants with Prenatal Cannabis Exposure.” The Office of Human Research Protections issued a decision against opening a case on this research, and we are asking you, as the Secretary of Health and Human Services, to overturn that decision based on the scientific concerns we outline in this letter.

Women who are in their first trimester of a pregnancy, who are frequent users of marijuana for morning sickness, are being recruited. The study seeks to assess the damage marijuana prenatal exposure may have on the babies by means of various testing, including an MRI scan of the infants at six months of age. The recruited women will receive $300.00 + for their participation. The study is solely funded by NIDA. This study calls into question serious issues over human rights and raises ethical questions, including mandatory reporting pertaining to substance abuse in pregnancy. This open letter seeks to gather support from you in seeing that this study is re-evaluated at the federal level. The study’s website is at the following link: https://depts.washington.edu/klab/infoMM.html

We are of the view that the Kleinhans study does not meet the requirements set forth by the Office of Human Research Protections (https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr46/ ): “Subpart B presumption that pregnant women may be included in research, provided certain conditions are met. According to Subpart B, the permissibility of research with pregnant women hinges on a judgment of the potential benefits and risks of the research. Approval of proposed research carrying no “prospect of direct benefit” to the woman or fetus requires that the risk to the fetus be judged “not greater than minimal”. Fetal risk that exceeds that standard is permissible only when the proposed research offers a prospect of direct benefit to the pregnant woman, the fetus, or both.

Notably, if the proposed research does not fit within either of those two parameters, Subpart B offers an additional mechanism at the national level for approval by the Secretary of Health and Human Services.”

The federal definition of minimum risk reads: “That the magnitude and probability of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” Although the primary harm at issue is exposure to marijuana, the use of MRI or fMRI has not yet been proven safe for otherwise healthy infants, where an unknown risk would come with no benefit, as there is no diagnosis being sought. The UW study consent form reads on page 3:“There are no known side effects associated with MRI or fMRI when earphones are used to protect your hearing.” …. “There may be risks associated with the use of magnetic resonance which are not known at this time.” It is precisely questions about the potential for MRI risks that should be investigated in an animal model first. In principle, any study that recruits subjects and then tracks the consequences of drug transfer to a developing fetus should be carried out in animal models first, and not in humans until the animal results point towards safety. The evidence of decades of research on marijuana in pregnancy does not point to safety but rather to risk and harm.

Two basic principles in bioethics are relied upon to determine the merit of research that involves human subjects: Is the study necessary and can the research be done without the use of human subjects? There now exists a significant body of scientific evidence that warrants and justifies warning women not to use marijuana products at pre-conception, while pregnant, or breast-feeding. The University of Washington study is not necessary to conclude that marijuana use is associated with risk to the child (and also the mother). The National Academies, a lead authority, concluded in a scientific literature review in 2017: There is substantial evidence of a statistical association between maternal cannabis smoking and lower birth weight of the offspring. Studies have already shown that prenatal use is associated with a 50 percent increased likelihood of low birth weight. The Surgeon General’s advisory of August 29, 2019 is also relied upon here. What is the “necessity” that this study addresses? The conclusion has already been made by the findings of science – pregnant women should refrain from marijuana use in order to protect the life and health of their child.

Yet, in spite of existing scientific literature of concern, a highly misleading recruitment statement appears on the University of Washington study’s website introductory page: “We do not expect to find anything of medical concern during the infant MRI scans…If you’re interested in helping us learn more about whether cannabis is safe to use for morning sickness, click the Sign Up button and let us know!” Their lack of concern about the potential for adverse medical outcomes directly contradicts the findings of Grewen et al. (2015) which similarly evaluated postnatal outcomes using MRI scans on infants that had been exposed to marijuana in utero. As compared to controls, the exposed infants showed hypoconnectivity between brain regions: ” Marijuana-specific differences were observed in insula and three striatal connections: anterior insula–cerebellum, right caudate–cerebellum, right caudate–right fusiform gyrus/inferior occipital, left caudate–cerebellum. +MJ neonates had hypo-connectivity in all clusters compared with −MJ and CTR groups.” While an imperfect study because the cases included a proportion of women in the case group who used not only marijuana but also alcohol, tobacco, opiates and SSRIs, one of the two control groups was matched to the cases for use of those drugs, while the other was completely drug free. Notably, work in an animal model by Tortoriello et al. (2014) presents a plausible mechanism for the observed effect of marijuana seen between cases and controls. The combined evidence points towards harm, and confirmation could easily be sought in an animal model that parallels the intent of the University of Washington study.

Furthermore, the ethics are clearly different between the Kleinhans et al. and Grewen et al. studies, because unlike the protocol for the former, the study of Grewen et al. did not recruit women while the fetus was developing but recruited shortly before or after the time of birth. Being unaware of marijuana use until the time of birth, the researchers could not intervene to encourage abstinence for the sake of the fetus, whereas the University of Washington team could intervene, but their protocols do not allow them to. As a further point of distinction, the University of Washington protocol states that infants enrolled in the study will be screened and excluded if they have been in an NICU for 24 hours. This will, for obvious reasons, result in a biased outcome in reporting overall harm from marijuana use during pregnancy.

Typical morning sickness affects up to 91% of pregnancies (Castillo and Phillippi, 2015), and is regarded by many medical practitioners as being a reflex protecting against consumption of dangerous foods or beverages, as well as a sign of a healthy pregnancy because the absence of morning sickness is associated with a higher rate of miscarriage (reviewed by Sherman and Flaxman, 2002). The rare condition when morning sickness becomes pathologic, hyperemesis gravidarum, affects on average 1.1% of pregnancies, and is defined as a loss of 5% or more of the pre-pregnancy weight (Castillo and Phillippi, 2015). Maintenance of fluid and electrolyte balance may become problematic in this situation and pharmacologic intervention may become necessary, both for the health of the mother and the baby. To date, the serious documented outcomes include an increased risk for preterm births and low birth weight (Dodds et al., 2006).

Thus, if the Kleinhans study were to be proposing to recruit only those with hyperemesis gravidarum, the ethics might be more favorable. They would, however, have to exclude women whose marijuana use may have triggered the hyperemesis, which may occur in a subset of pregnant users (Alaniz et al., 2015). The study recruitment website is definitely remiss in not making that possibility clear to those interested in enrolling, and the research protocol describes no effort to ascertain if marijuana might be triggering hyperemesis in their study subjects.

In summary, there is already sufficient scientific evidence to answer the question as to whether or not marijuana is safe to use for typical morning sickness. That answer is no. Please see additional references for numerous research publications showing harm at the end of this letter.
Complaints have been filed with NIDA, The University of Washington, The World Medical Association regarding the Helsinki Declaration, The Office of Human Research Protections, and two doctors have filed a human rights complaint on behalf of the children involved. Complaint documents will be forwarded on request.

Thank you for your time in reviewing this serious situation.

Best regards,
Pamela McColl
Child Rights Activist
pjmccoll@shaw.ca

and

Christine L. Miller, Ph.D.
Neuroscientist
MillerBio
6508 Beverly Rd
Baltimore, Maryland 21239
cmiller@millerbio.com

et al.

Correspondence with the OHRP in regards to the University of Washington study began in September
of 2019. On October an email was received from the OHRP to Pamela McColl:
October 25, 2019

Hello,
OHRP has reviewed the study and will not be opening a case.
Sincerely,
Division of Compliance Oversight OHRP

September 25, 2019
“OHRP is now reviewing your complaint and this study. We are currently gathering the information about the research being conducted before a full review is started. Once OHRP completes a full review of the study, the research conducted and the study’s approval process, we will contact you with our findings. Please remember, this does not mean you can’t contact OHRP again before we finish the full review. You can contact us using this email address to update your complaint at any time.
Thank-you,
Division of Compliance Oversight (OHRP)

September 17, 2019
Thank you for contacting the Office for Human Research Protections (OHRP). OHRP has responsibility for oversight of compliance with the U.S. Department of Health and Human Services (HHS) regulations for the protection of human research subjects (see 45 CFR Part 46 at
www.hhs.gov/ohrp/regulations-and-policy/guidance/index.html

In carrying out this responsibility, OHRP reviews allegations of noncompliance involving human subject research projects conducted or supported by HHS or that are otherwise subject to the regulations, and determines whether to conduct a for-cause compliance evaluation. For further details see OHRP’s guidance, “Compliance Oversight Procedures for Evaluating Institutions,” at www.hhs.gov/ohrp/compliance-and-reporting/evaluating-institutions/index.html.

OHRP has jurisdiction only if the allegations involve human subject research (a) conducted or supported by HHS, or (b) conducted at an institution that voluntarily applies its Assurance of Compliance to all research regardless of source of support. Since this requirement appears to be met by the circumstances described in your email, OHRP appears to have jurisdiction.
Sincerely,
Division of Compliance Oversight
cc. Surgeon General Jerome Adams
cc. Director NIDA Dr. Nora Volkow

In-text citations:
Alaniz VI, Liss J, Metz TD, Stickrath E. Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in pregnancy. Obstet Gynecol. 2015 Jun;125(6):1484-6.
Castillo MJ, Phillippi JC. Hyperemesis gravidarum: a holistic overview and approach to clinical assessment and management. J Perinat Neonatal Nurs. 2015;29(1):12-22.
Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006;107(2, pt 1):285–292.
Grewen K, Salzwedel AP, Gao W. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure. Front Hum Neurosci. 2015;9:601.
Sherman PW, Flaxman SM. Nausea and vomiting of pregnancy in an evolutionary perspective. Am J Obstet Gynecol. 2002;186(5 Suppl Understanding):S190-7.
The National Academies of Sciences, Engineering, and Medicine, 2017, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies Press, Washington, D.C. 20001
Tortoriello G, et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 2014;33(7):668-85.

Additional references on specific neonatal outcomes:
Lower birth weight, animal studies
Benevenuto SG et al., Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice. Toxicology. 2017;376:94-101.
“Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight…..females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group”

Lower birth weight, human studies
Gunn,JKL, Rosales CB, Center KE, Nunez A, Gibson SJ, Christ C, and Ehiri EJ. Prenatal exposure to cannabis and maternal and child health outcomes: A systematic review and meta-analysis. BMJ Open 2016; 6(4):e009986.
“Infants exposed to cannabis in utero had a decrease in birth weight (low birth weight pOR=1.77: 95% CI 1.04 to 3.01; pooled mean difference (pMD) for birth weight=109.42 g: 38.72 to 180.12) compared with infants whose mothers did not use cannabis during pregnancy. Infants exposed to cannabis in utero were also more likely to need placement in the neonatal intensive care unit compared with infants whose mothers did not use cannabis during pregnancy (pOR=2.02: 1.27 to 3.21).”
Brown SJ, Mensah FK, Ah Kit J, Stuart-Butler D, Glover K, Leane C, Weetra D, Gartland D, Newbury J, Yelland J. Use of cannabis during pregnancy and birth outcomes in an Aboriginal birth cohort: a crosssectional, population-based study. BMJ Open. 2016;6(2):e010286.
“Controlling for education and other social characteristics, including stressful events/social health issues did not alter the conclusion that mothers using cannabis experience a higher risk of negative birth outcomes (adjusted OR for odds of low birth weight 3.9, 95% CI 1.4 to 11.2).”
Fergusson, D. M., L. J. Horwood, and K. Northstone. 2002. Maternal use of cannabis and pregnancy outcome. British Journal of Obstetrics and Gynaecology 109(1):21–27.
“Over 12,000 women expecting singletons at 18 to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of Pregnancy and Childhood……the babies of women who used cannabis at least once per week before and throughout pregnancy were 216g lighter than those of non-users.”

Preterm birth, animal studies
Wang H, Xie H, Dey SK. Loss of cannabinoid receptor CB1 induces preterm birth. PLoS One. 2008;3(10):e3320.
“CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice…. CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis.”

Preterm birth, human studies
Luke S, Hutcheon J, Kendall T. Cannabis Use in Pregnancy in British Columbia and Selected Birth Outcomes. J Obstet Gynaecol Can. 2019;41(9):1311-1317.
“Using cannabis in pregnancy was associated with a 47% increased risk of SGA (adjusted OR 1.47; 95% CI 1.33–1.61), a 27% increased risk of spontaneous preterm birth (adjusted OR 1.27; 95% CI 1.14–1.42), and a 184% increased risk of intrapartum stillbirth (adjusted HR [aHR] 2.84; 95% CI 1.18–6.82).”
Corsi DJ, Walsh L, Weiss D, Hsu H, El-Chaar D, Hawken S, Fell DB, Walker M. Association Between Selfreported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes. JAMA. 2019;322(2):145-152.
“In a cohort of 661 617 women…. The crude rate of preterm birth less than 37 weeks’ gestation was 6.1%among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95%CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98%(95%CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95%CI, 1.45-1.61]), placental abruption (1.6%vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3%vs 13.8%; RR, 1.40 [95%CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95%CI, 1.13-1.45]).”
Saurel-Cubizolles MJ, Prunet C, Blondel B. Cannabis use during pregnancy in France in 2010. BJOG. 2014;121(8):971-7.
“Cannabis users had higher rates of spontaneous preterm births: 6.4 versus 2.8%, for an adjusted odds ratio (aOR) of 2.15 (95% CI 1.10–4.18).”
Leemaqz SY, Dekker GA, McCowan LM, Kenny LC, Myers JE, Simpson NA, Poston L, Roberts CT;

SCOPE Consortium. Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications. Reprod Toxicol. 2016;62:77-86. “continued maternal marijuana use at 20 weeks’ gestation was associated with” spontaneous preterm birth “independent of cigarette smoking status [adj OR2.28 (95% CI:1.45–3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41–3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks’ gestation had a greater effect size [adj OR 5.44 (95% CI 2.44–12.11)].”

Impacts on the neonatal immune system, animal study
Zumbrun EE et al. Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring. J Neuroimmune Pharmacol. 2015; 10(2):245-54.
“Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens

Impacts on cortical wiring and development, animal studies
Tortoriello G, et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 2014;33(7):668-85.
“Here, we show that repeated THC exposure disrupts endocannabinoid signaling, particularly the temporal dynamics of CB1 cannabinoid receptor, to rewire the fetal cortical circuitry….these data highlight the maintenance of cytoskeletal dynamics as a molecular target for cannabis”
DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, Dow-Edwards D, Hurd YL. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011 Oct 15;70(8):763-9.
“we exposed pregnant rats to THC and examined the epigenetic regulation of the NAc Drd2 gene in their offspring at postnatal day 2, comparable to the human fetal period studied, and in adulthood…. Decreased Drd2 expression was accompanied by reduced D2R binding sites and increased sensitivity to opiate reward in adulthood”
Rodríguez de Fonseca F, Cebeira M, Fernández-Ruiz JJ, Navarro M, Ramos JA. Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons. Neuroscience. 1991;43(2-3):713-23.
“Perinatal exposure to cannabinoids altered the normal development of nigrostriatal, mesolimbic and tuberoinfundibular dopaminergic neurons, as reflected by changes in several indices of their activity”.

Impacts on cortical wiring and development, human studies
Grewen K, Salzwedel AP, Gao W. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure. Front Hum Neurosci. 2015;9:601.

“+MJ (marijuana-exposed) neonates had hypo-connectivity in all clusters compared with –MJ (marijuana unexposed) and CTR (control) groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs
involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use.”
El Marroun H, Tiemeier H, Franken IH, Jaddoe VW, van der Lugt A, Verhulst FC, Lahey BB, White T. Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A Prospective Neuroimaging Study in Young Children. Biol Psychiatry. 2016;79(12):971-9.
“prenatal cannabis exposure was associated with differences in cortical thickness….. it may be possible that the frontal cortex in cannabis-exposed children undergoes altered neurodevelopmental maturation (i.e., having differences in cortical trajectories) as compared with
nonexposed control subjects”
Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL. In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry. 2004; 56:909–915.
“Adjusting for various covariates, we found a specific reduction, particularly in male fetuses, of the D(2) mRNA expression levels in the amygdala basal nucleus in association with maternal marijuana use. The reduction was positively correlated with the amount of maternal marijuana intake during pregnancy.”

Received by email

I, Surgeon General VADM Jerome Adams, am emphasizing the importance of protecting our Nation from the health risks of marijuana use in adolescence and during pregnancy. Recent increases in access to marijuana and in its potency, along with misperceptions of safety of marijuana endanger our most precious resource, our nation’s youth.

BE PREPARED. GET NALOXONE. SAVE A LIFE.

Background

Marijuana, or cannabis, is the most commonly used illicit drug in the United States. It acts by binding to cannabinoid receptors in the brain to produce a variety of effects, including euphoria, intoxication, and memory and motor impairments. These same cannabinoid receptors are also critical for brain development. They are part of the endocannabinoid system, which impacts the formation of brain circuits important for decision making, mood and responding to stress.

Marijuana and its related products are widely available in multiple forms. These products can be eaten, drunk, smoked, and vaped. Marijuana contains varying levels of delta-9-tetrahydrocannabinol (THC), the component responsible for euphoria and intoxication, and cannabidiol (CBD). While CBD is not intoxicating and does not lead to addiction, its long-term effects are largely unknown, and most CBD products are untested and of uncertain purity.

Marijuana has changed over time. The marijuana available today is much stronger than previous versions. The THC concentration in commonly cultivated marijuana plants has increased three-fold between 1995 and 2014 (4% and 12% respectively). Marijuana available in dispensaries in some states has average concentrations of THC between 17.7% and 23.2%. Concentrated products, commonly known as dabs or waxes, are far more widely available to recreational users today and may contain between 23.7% and 75.9% THC.

The risks of physical dependence, addiction, and other negative consequences increase with exposure to high concentrations of THC and the younger the age of initiation. Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis. Edible marijuana takes time to absorb and to produce its effects, increasing the risk of unintentional overdose, as well as accidental ingestion by children and adolescents. In addition, chronic users of marijuana with a high THC content are at risk for developing a condition known as cannabinoid hyperemesis syndrome, which is marked by severe cycles of nausea and vomiting.

This advisory is intended to raise awareness of the known and potential harms to developing brains, posed by the increasing availability of highly potent marijuana in multiple, concentrated forms. These harms are costly to individuals and to our society, impacting mental health and educational achievement and raising the risks of addiction and misuse of other substances.  Additionally, marijuana use remains illegal for youth under state law in all states; normalization of its use raises the potential for criminal consequences in this population. In addition to the health risks posed by marijuana use, sale or possession of marijuana remains illegal under federal law notwithstanding some state laws to the contrary.

Watch the Surgeon General Answer FAQs on Marijuana

Marijuana Use during Pregnancy

Pregnant women use marijuana more than any other illicit drug. In a national survey, marijuana use in the past month among pregnant women doubled (3.4% to 7%) between 2002 and 2017. In a study conducted in a large health system, marijuana use rose by 69% (4.2% to 7.1%) between 2009 and 2016 among pregnant women. Alarmingly, many retail dispensaries recommend marijuana to pregnant women for morning sickness.

Marijuana use during pregnancy can affect the developing fetus.

• THC can enter the fetal brain from the mother’s bloodstream.
• It may disrupt the endocannabinoid system, which is important for a healthy pregnancy and fetal brain development
• Studies have shown that marijuana use in pregnancy is associated with adverse outcomes, including lower birth weight.
• The Colorado Pregnancy Risk Assessment Monitoring System reported that maternal marijuana use was associated with a 50% increased risk of low birth weight regardless of maternal age, race, ethnicity, education, and tobacco use.

The American College of Obstetricians and Gynecologists holds that “[w]omen who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Women reporting marijuana use should be counseled about concerns regarding potential adverse health consequences of continued use during pregnancy”. In 2018, the American Academy of Pediatrics recommended that “…it is important to advise all adolescents and young women that if they become pregnant, marijuana should not be used during pregnancy”.

Maternal marijuana use may still be dangerous to the baby after birth. THC has been found in breast milk for up to six days after the last recorded use. It may affect the newborn’s brain development and result in hyperactivity, poor cognitive function, and other long-term consequences. Additionally, marijuana smoke contains many of the same harmful components as tobacco smoke. No one should smoke marijuana or tobacco around a baby.

Marijuana Use during Adolescence

Marijuana is also commonly used by adolescents, second only to alcohol. In 2017, approximately 9.2 million youth aged 12 to 25 reported marijuana use in the past month and 29% more young adults aged 18-25 started using marijuana. In addition, high school students’ perception of the harm from regular marijuana use has been steadily declining over the last decade. During this same period, a number of states have legalized adult use of marijuana for medicinal or recreational purposes, while it remains illegal under federal law. The legalization movement may be impacting youth perception of harm from marijuana. 

The human brain continues to develop from before birth into the mid-20s and is vulnerable to the effects of addictive substances. Frequent marijuana use during adolescence is associated with:

• Changes in the areas of the brain involved in attention, memory, decision-making, and motivation. Deficits in attention and memory have been detected in marijuana-using teens even after a month of abstinence.
• Impaired learning in adolescents. Chronic use is linked to declines in IQ, school performance that jeopardizes professional and social achievements, and life satisfaction.
• Increased rates of school absence and drop-out, as well as suicide attempts.

Risk for and early onset of psychotic disorders, such as schizophrenia. The risk for psychotic disorders increases with frequency of use, potency of the marijuana product, and as the age at first use decreases. 

• Other substance use. In 2017, teens 12-17 reporting frequent use of marijuana showed a 130% greater likelihood of misusing opioids23.

Marijuana’s increasingly widespread availability in multiple and highly potent forms, coupled with a false and dangerous perception of safety among youth, merits a nationwide call to action. 

You Can Take Action

No amount of marijuana use during pregnancy or adolescence is known to be safe. Until and unless more is known about the long-term impact, the safest choice for pregnant women and adolescents is not to use marijuana.  Pregnant women and youth–and those who love them–need the facts and resources to support healthy decisions. It is critical to educate women and youth, as well as family members, school officials, state and local leaders, and health professionals, about the risks of marijuana, particularly as more states contemplate legalization.

Science-based messaging campaigns and targeted prevention programming are urgently needed to ensure that risks are clearly communicated and amplified by local, state, and national organizations. Clinicians can help by asking about marijuana use, informing mothers-to-be, new mothers, young people, and those vulnerable to psychotic disorders, of the risks. Clinicians can also prescribe safe, effective, and FDA-approved treatments for nausea, depression, and pain during pregnancy. Further research is needed to understand all the impacts of THC on the developing brain, but we know enough now to warrant concern and action. Everyone has a role in protecting our young people from the risks of marijuana.

Information for Parents and Parents-to-be

You have an important role to play for a healthy next generation.

• Review the facts to understand the risks associated with marijuana use during pregnancy.
• Check out these Frequently Asked Questions  about marijuana use and pregnancy.
• Learn about marijuana safety for children and pregnant and breastfeeding women.
• Start a conversation with your kids: Marijuana: Facts Parents Need to Know.
• Keep your adolescent from using marijuana and other drugs: Keeping Youth Drug Free – PDF.
• Watch the Message to Parents from NIH/NIDA 

Information for Youth:

You have an important role to play for a healthy next generation.

• Want to know how marijuana affects brain development? Get the facts. 
• Learn key techniques on how to resist peer pressure: Above the Influence .
• Learn how to help friends stop using marijuana with Letter to Teens
• Get around-the-clock free advice and referrals: Substance Abuse and Mental Health Administration (SAMHSA) National Helpline (1-800-662-HELP (4357).

Information for States, Communities, Tribes, and Territories:

You have an important role to play for a healthy next generation.

• Learn how communities and schools can act: Preventing Marijuana Use among Youth & Young Adults.
• Find key messages for communities at www.samhsa.gov/marijuana. 
• Get training and educational resources for your community: Prevention Technology Transfer Centers.

Information for Health Professionals:

You have an important role to play for a healthy next generation.

• Learn how you can integrate marijuana education into prenatal care visits: Marijuana Pregnancy & Breastfeeding Guidance – PDF.
• Get advice on talking with adolescents and parents about marijuana use from the American Academy of Pediatrics guidance for clinicians .
• Read the American College of Obstetricians and Gynecologists position on Marijuana use during pregnancy and lactation .

Source: Surgeon General’s Advisory: Marijuana Use & the Developing Brain | HHS.gov August 2019

Police forces in the province collected 795 blood samples from motorists suspected of driving while under the influence.

One year after the legalization of recreational use of cannabis in Canada, the black market for the drug — as well as its use behind the wheel — continues to keep Quebec police forces busy.

In 2018, police collected 795 blood samples from motorists suspected of driving while under the influence, and sent them to Quebec’s medical legal centre for processing. That’s 254 more than in the previous year.

The presence of cannabis was detected in 46 per cent of those cases.

The Sûreté du Québec says cannabis is the most commonly detected drug in its traffic stops.

The provincial force said that since legalization, cannabis was detected in the systems of 113 persons pulled over for impaired driving, compared with 73 cases a year earlier — an increase of 54 per cent.

More than 670 officers trained in drug use evaluation have been deployed across the province.

In a statement issued Thursday detailing its operations over the past year, the SQ said it had opened 1,409 investigations into the illegal production, supply and distribution of cannabis, which led to 1,458 warrants being executed and charges filed against 1,403 individuals.

Meanwhile, raids on illegal outdoor cannabis fields were carried out in August and September, and saw 37,000 plants seized.

Over the past year, the SQ seized 71,500 cannabis plants, 161 kilograms of cannabis, 15.8 kilograms of cannabis oil and resin, 23,460 units of edible cannabis and $180,000 in cash.

Source:  https://montrealgazette.com/news/local-news/quebec-pot-arrests-behind-the-wheel-up-54-since-legalization October 2019

The 2018 Monitoring the Future College Students and Young Adults survey shows trends in the use of marijuana, alcohol, nicotine, and synthetic drugs in college students and non-college peers.

Marijuana Use

Annual Marijuana Use at Historic Highs among College and Non-College Peers*
Marijuana use is nearly the same for college students and their non-college peers at about 43%. This is approximately a 7% increase over five-years for college students. These rates for both groups are the highest in 35 years.

Daily/Near Daily Use** of Marijuana Twice as High among Non-College Group
Approximately one in nine non-college respondents reporting daily or near daily use, (11.1%) compared to about one in 17 college students (5.9%).

** Used on 20 or more occasions in the past 30 days

Past Month Nicotine Vaping Doubles Among College Students

This jump is among the greatest one-year increase seen for any substance in the history of the survey.
Between 2017 and 2018, nicotine vaping increased in college students from 6.1% to 15.5% and from 7.9% to 12.5% in non-college adults. 

Rx Drug Misuse has Mixed Results

Rx Opioid Misuse: Significant Five Year Drop in Both Groups
Past year misuse of prescriptions opioids dropped from 5.4% in 2013 to 2.7% among college students and from 9.6% in 2013 to 3.2% among non-college adults.

Adderall® Misuse: Significant Gender Differences
Past year misuse rates of Adderall® were 14.6% among college men and 8.8% among college women.  Rates were higher, however, in non-college women than in non-college men (10.1% and 5.3% respectively).

Overall Adderall® misuse is higher among college students (11.1%) than their non-college peers (8.1%)

Binge Drinking (five or more drinks in a row in the past two weeks) Fell Below 30% for the First Time among College Students

In 2018, binge drinking declined among college students (28%) and non-college adults (25%).

*Please note, the college-age adults are ages 19-22.

Source: Drug and Alcohol Use in College-Age Adults in 2018 | National Institute on Drug Abuse (NIDA) (nih.gov) September 2019

• Medical Profession.  Many professional organizations have made strong statements warning against widespread cannabis use. e.g. AMA, RACGP, AAP, ACOG, British Lung Foundation.

• Common Pattern.  The almost ubiquitous pattern in which medical cannabis is used today is to treat decades long cannabis addiction, with the other indications serving as mere “tickets” to engage whilst simultaneously avoiding legal censure.

• Parallel Drug Approval Pathway.  It is obvious that whilst all other drugs are held to a strict approvals and regulatory pathway cannabis products are held to no serious control whatsoever with the industry in an effectively unregulated exponential growth phase.

• Limited Benefits. Despite the international rhetoric of many governments and the  cannabis industry there is either nil or very poor evidence for the efficacy of the vast majority of cannabinoid products in the management of  most indications presenting to GPs  (Ref RACGP Review).

• Known Harms.  Alternately, there is increasing direct and indirect evidence from cellular, mechanistic, case data and epidemiological studies of “likely” harm from cannabis, both within and across generations (epigenetics). This is supported by large epidemiological studies, confirming increased cancers and neonatal congenital abnormalities in areas of increased cannabinoid use, not dissimilar from those used to identify links between tobacco or alcohol and morbidities.  Numerous aging pathologies are also accelerated.

• Further Harms.
  1. Gateway role – Into harder drugs and criminal lifestyle is now well established by studies in numerous countries.  Whilst few cannabis users progress to harder drugs, virtually all users of harder drugs have used cannabis, with much higher rates of drug and criminal progression amongst ever users of cannabis.
  2. Adult Brain – Most major psychiatric syndromes have been linked with cannabis viz: sedation, amotivational state, anxiety, PTSD, serious mental disorders, depression, psychosis, bipolar disorder, schizophrenia, suicidal thoughts and completed suicides.  Also linked with homicide and violence and over 70 mass shootings in USA thought to be linked with aggression (seen in both cannabis withdrawal and intoxication), impaired judgement and psychosis
  3. Child Brain – ADHD-like and autism-like features; extreme aggression; impaired cortical processing; learning difficulties; smaller brain; microcephaly; anencephaly (which causes death within hours)
  4. Chest disease – COPD, chronic bronchitis, emphysema, lung cysts, elevated residual volume, premalignant changes in upper and lower airways
  5. Immunomodulation – Both immunosuppression and immunostimulation are described mediated via T-cells, B-cells, NK Cells, T-reg cells, antibodies and cytokines
  6. Endocrinopathy – Central and peripheral hypogonadism, Prolactin elevated
  7. Cardiovascular  – accelerated coronary artery and atherosclerotic disease; strongly arrythmogenic (many tachyarrhythmias both atrial and ventricular)

• Genetic Toxicity.  These include gestationally and neonatal congenital abnormalities, cancers both childhood and adult, and the occurrence of premature age-related morbidities, and powerful direct effects on the aging process etc.

• Known Mechanisms.  These findings are underpinned by clear cellular mechanistic studies on how cannabinoids (both THC and CBD based) can cause the above by interfering  with normal cellular and body functions creating antecedents of disease. This of course is not surprising given the increasing understanding of the role of endogenous cannabinoids in normal development, body functioning, and cellular reproduction and maintenance, chromosomes, gene maintenance and control (epigenome) and that use of large doses or prolonged exogenous cannabinoids can significantly disrupt these functions.

• “Do No Harm.”  Given the aforementioned, it is clear that caution needs to be applied to the medical use of cannabinoids, that although in the most positive interpretation may have a nominal impact managing morbidities, may in turn cause greater harm transgenerationally.

• Multigenerational Impacts Genetic and epigenetic effects are believed to persist for at least three to four generations.  Cannabinoids have been shown to be driving several childhood (and thus cross-generational) cancers including total childhood cancer.  Cannabis, THC and cannabidiol have been shown to be linked with the cancers of the: breast, prostate, ovary and testis showing carcinogenesis to the reproductive organs.  Also many birth defects including the absence of arms and legs and congenital brain, face,  and heart defects.  Also aging of the sperm and ovum themselves in rodents and humans.

• Rigorous Trials – Evidence Base.  It is therefore not only reasonable but essential that each cannabinoid product marketed should be assessed by the established international standards for pharmaceutical development, and to which all other pharmaceutical products, prior to being released and used in populations must conform.  There is need for a robust evidence base.  At present cannabis is not performing impressively in hundreds of clinical trials.  In the case of cannabinoids this must include rigorous and long term tests of genetic, epigenetic and epitranscriptomic toxicity including: genotoxicity, carcinogenicity, mutagenicity, teratogenicity and gametotoxicity in both sexes.

Source: https://pubmed.ncbi.nlm.nih.gov/

Nearly 10% of cannabis users in the United States report using it for medicinal purposes.
As of August 2019, 33 states and the District of Columbia have initiated policies allowing the use of cannabis or cannabinoids for the management of specific medical conditions.
Yet, the federal government still classifies cannabis as illegal, complicating its medical use and research into its effectiveness as a treatment for the various conditions purported to benefit from cannabis pharmacotherapy. Because of this conflict and restrictions on cannabis research, evidence of the efficacy of cannabis to manage various diseases is often lacking.

This article updates a review published in the June 23, 2015, issue of JAMA2 and describes newer evidence regarding what is known and not known about the efficacy of cannabis and cannabinoids for managing various conditions.

Indications for Therapeutic Use Approved by the US Food and Drug Administration
Cannabis has numerous cannabinoids, the most notable being tetrahydrocannabinol, which accounts for its psychoactive effects. Individual cannabinoids have unique pharmacologic profiles enabling drug development to manage various conditions without having the cognitive effects typically associated with cannabis.

Only a few cannabinoids have high-quality evidence to support their use and are approved for medicinal use by the US Food and Drug Administration (FDA). The cannabinoids dronabinol and nabilone were approved by the FDA for chemotherapy-induced nausea and vomiting in 1985, with dronabinol gaining an additional indication for appetite stimulation in conditions that cause weight loss, such as AIDS, in 1992. Recently, a third cannabinoid, cannabidiol (CBD), was approved by the FDA for the management of 2 forms of pediatric epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, based on the strength of positive randomized clinical trials (RCTs).

Other Medical Indications
Cannabinoids are often cited as being effective for managing chronic pain. The National Academies of Science, Engineering, and Medicine examined this issue and found that there was conclusive or substantial evidence that cannabis or cannabinoids effectively managed chronic pain, based on their expert committee’s assessment that the literature on this topic had many supportive findings from good-quality studies with no credible opposing findings.

The panel relied on a single meta-analysis of 28 studies, few of which were from the United States, that assessed a variety of diseases and compounds. Although they concluded that cannabinoids effectively managed pain, the CIs associated with these findings were large, suggesting unreliability in the meta-analysis results.
A more recent meta-analysis of 91 publications found cannabinoids to reduce pain 30% more than placebo (odds ratio, 1.46 [95% CI, 1.16 1.84]), but had a number needed to treat for chronic pain of 24 (95% CI, 15-61) and a number needed to harm of 6 (95% CI, 5-8).While a moderate level of evidence supports these recommendations, most studies of the efficacy of cannabinoids on pain are for neuropathic pain, with relatively few high-quality studies examining other types of pain. Taken together, at best, there is only inconclusive evidence that cannabinoids effectively manage chronic pain, and large numbers of patients must receive treatment with cannabinoids for a few to benefit, while not many need to receive treatment to result in harm.
There is strong evidence to support relief of symptoms of muscle spasticity resulting from multiple sclerosis from cannabinoids as reported by patients, but the association is much weaker when outcomes are measured by physicians. There is insufficient evidence to support or refute claims that cannabinoids provide relief for spinal cord injury–related muscle spasms.

Recent Clinical Trials
Two multicenter, international trials with substantial numbers of patients (n = 120 and n = 171) demonstrated the efficacy of CBD as an add-on drug to manage some seizure disorders. Over 14 weeks, 20mg/kg of CBD significantly reduced the median frequency of convulsive seizures in children and young adults with Dravet syndrome as well as the estimated median difference in monthly drop seizures between CBD and placebo in patients with Lennox-Gastaut syndrome. Although promising, these results were found in relatively uncommon disorders and the studies were limited by the use of subjective end points and incomplete blinding that is typical of cannabinoid studies because these drugs have readily identifiable side effects.
Numerous other medical conditions, including Parkinson disease, posttraumatic stress disorder, and Tourette syndrome, have a hypothetical rationale for the use of cannabis or cannabinoids as pharmacotherapy based on cannabinoid effects on spasticity, anxiety, and density of cannabinoid receptors in areas implicated in development of tics, such as the basal ganglia and cerebellum. The strength of the evidence supporting the use of cannabinoids for these diseases is weak because most studies of patients with these diseases have been small, often uncontrolled, or crossover studies.

Few pharmaceutical companies are conducting cannabinoid trials. Thus, it is not likely that additional cannabinoids will be approved by the FDA in the near future. Public interest in cannabis and cannabinoids as pharmacotherapy continues to increase, as does the number of medical conditions for which patients are utilizing cannabis and CBD, despite insufficient evidence to support this trend.

Neurologic Adverse Effects Are Better Defined Than Physical Adverse Effects
Acute cannabis use is associated with impaired learning, memory, attention, and motor coordination, areas that can affect important activities of daily living, such as driving. Acute cannabis use can also affect judgment, potentially resulting in users making risky decisions that they would not otherwise make. While there is consensus that acute cannabis use results in cognitive deficits, residual cognitive effects persisting after acute intoxication are still debated, especially for individuals who used cannabis regularly as adolescents.

Chronic cannabis use is associated with an increased risk of psychiatric illness and addiction. There is a significant association— possibly a causal relationship—between cannabis use and the development of psychotic disorders, such as schizophrenia, particularly among heavy users. Chronic cannabis use can lead to cannabis use disorder (CUD) and contributes to impairment in work, school, and relationships in up to 31% of adult users.  Regular cannabis use at levels associated with CUD (near-daily use of more than one eighth ounce of cannabis per week) is associated with worsening functional status, including lower income, greater need for socio-economic assistance, criminal behavior, unemployment, and decreased life satisfaction.

Cannabis use is associated with adverse perinatal outcomes as well; a 2019 study showed the crude rate of preterm birth was 12.0% among cannabis users and 6.1% among nonusers (risk difference, 5.88% [95% CI, 5.22%-6.54%]).

Inadequate Evidence Supporting the Use of Cannabinoids for Many Medical Conditions
The quality of the evidence supporting the use of cannabinoids is suboptimal. First, studies assessing pain and spasticity are difficult to conduct, in part because of heterogeneity of the outcome measures used in these studies. Second, most RCTs that have evaluated cannabinoid clinical outcomes were small, with fewer than 100 participants in each, and small trials may overestimate treatment effects. Third, the timeframe for most studies is too short to assess the long-term effects of these medications. Fourth, tolerance, withdrawal, and potential for drug-drug interactions may affect the usefulness of cannabis, and these phenomena are not well understood for cannabinoids.

The lack of high-quality evidence results in outsized claims of the efficacy of cannabinoids for numerous medical conditions. There is a need for well-designed, large, multisite RCTs of cannabis or cannabinoids to resolve claims of efficacy for conditions for which there are claims of efficacy not supported by high quality evidence, such as pain and spasticity.

Conclusions
Insufficient evidence exists for the use of medical cannabis for most conditions for which its use is advocated. Despite the lack of evidence, various US state governments have recommended cannabis for the management of more than 50 medical conditions. Physicians may be appropriately reticent to recommend medical cannabis for their patients because of the limited scientific evidence supporting its use or because cannabis remains illegal in federal law. Cannabis is useful for some conditions, but patients who might benefit may not get appropriate treatment because of insufficient awareness regarding the evidence supporting its use or confusion from federal law deeming cannabis illegal.

Source: Medical Use of Cannabis in 2019 | Clinical Pharmacy and Pharmacology | JAMA | JAMA Network August 2019

Cannabis hyperemesis syndrome (CHS) is nothing new, but nonetheless lacks a diagnosis code. This means that nobody—including the Centers for Disease Control and Prevention, which is meant to track such things—knows the prevalence of the condition. It is, however, relatively rare. Medical sources say that it’s likely, as you’d expect, to become more common as nationwide cannabis use increases.

No one claims that CHS is lethal, but it is uncomfortable—and in an emergency room situation requires such medications as haloperidol, an antipsychotic, to relieve vomiting and pain. Business Insider recently reported the story of 29-year-old Alice Moon, who began using cannabis regularly to treat pain and nausea. She did so without problems for five years, but then began experiencing CHS symptoms monthly, and eventually weekly.

People who use any substance deserve access to relevant health information, without exaggeration in either direction. “Marijuana is somehow making millions violently sick” and “Mysterious Syndrome Related To Marijuana Use Begins To Worry Doctors” are two CHS-related news headlines from the past month alone. But CHS likely doesn’t affect millions, and it is less mysterious than some imply.

So this isn’t a Reefer Madness story, designed to scare people, nor a head-in-the-sand story, designed to appeal to those who see cannabis as a risk-free panacea.

Even pro-cannabis advocates agree that CHS exists. “It’s a diagnosis of exclusion,” Peter Grinspoon, MD, a primary care physician at an inner-city clinic in Boston, told Filter. Grinspoon is also on staff at Massachusetts General Hospital, teaches at Harvard Medical School, and authored the memoir Free Refills: A Doctor Confronts His Addiction (2016). “I’m not sure how you can really differentiate it from cyclic vomiting syndrome (CVS), idiopathic [unknown cause] vomiting, or just something else causing the vomiting—except for a cannabis history.”

Experts believe that the action of the cannabinoid THC on our CB1 receptors, which are found all over the body but mainly in the brain, produces the symptoms of CHS—though the amounts of THC required, the duration of use in months or years, and why some people experience CHS and not others, are still unexplained.

One thing everyone seems to agree on: CHS is caused by heavy long-term use of cannabis—i.e., it’s not a result of overdose or acute toxicity. And it has one unusual manifestation: People afflicted like to take many hot baths or showers for relief.

A study published last month, based on emergency room visits in a Colorado hospital, also found that CHS is more likely to be associated with smoked than edible cannabis. Of 2,567 ER visits that were at least partly attributed to cannabis use, 18 percent of patients who inhaled it were said to have CHS, versus 8.4 percent of those who ate it.

Emergency Physicians’ Experiences

 “It’s very dramatic—patients are sometimes writhing on the floor, and they’re vomiting so much. It’s a horrible syndrome,” said Andrew C. Meltzer, MD, associate professor in the Department of Emergency Medicine and Clinical Research Director of GWU School of Medicine and Health Sciences. “It’s very different from any other kind of vomiting thing, and very disruptive to the ED.”

And in the worst cases, “repeated aggressive vomiting can cause tears in the esophagus.”  

 Unlike gastroenteritis, with CHS there is no diarrhea, no fever and more of a hypersensitivity to pain in the abdomen, Meltzer told Filter. There is an “overlap” with cyclical vomiting syndrome (CVS), in that many symptoms are the same. Blood work might be needed to rule out pancreatitis and hepatitis, and some patients get radiology.

Toxicology testing, on the other hand, is not very useful, because so many people use marijuana without showing these symptoms. Rather, it’s important to get a history of the extent and duration of marijuana use from the patient, said Meltzer. “Confusion exists in the medical literature,” he noted. In addition, he believes there is a pervasive failure to recognize chronic cannabis use as a possible cause of vomiting.

“We’re still trying to figure out how to make them feel better,” said Meltzer of CHS patients. “Typical anti-emetics like Phenergan and Zofran don’t work. Instead, we use antipsychotics, like haloperidol.” In fact, if the haloperidol works, Meltzer views that as diagnostic of CHS in some ways. The heat from capsaicin rubbed on the abdomen also provides some relief from pain.

In the patients Meltzer has seen with CHS, all “would qualify as addicted” to cannabis, he said. He doesn’t recommend using morphine for CHS pain because of what he sees as the addiction risk in this population.

Some CHS patients can’t be treated with emergency room management alone. Meltzer said he had to admit one patient for dehydration, fluids replacement, renal insufficiency, and other problems. “But now we’re getting more used to how to manage this with haloperidol and even Ativan. They are sedated, they sleep, and they go home.”

“I don’t care what people do in their free time, but in the medical history I try to include things that are pertinent.”

Ryan Marino, MD, an emergency medicine physician and medical toxicologist at the University of Pittsburgh, sees CHS about two-to-three times a month—but acknowledges it could be more, because sometimes it’s hard to be sure.

“The big issue is [CHS] is under-recognized,” said Marino, agreeing with Meltzer. “So a lot of patients get unnecessary testing.” For someone who comes in with a lot of nausea and vomiting, and is young and otherwise healthy, he says it’s important to ask about their marijuana use.

“I try to be as non-judgemental as possible” in asking those questions, he said. “I don’t care what people do in their free time, but in the medical history I try to include things that are pertinent.”

With emergency patients, the differential diagnosis is crucial and must be done quickly. “When there’s belly pain, you worry about things that need surgery, like appendicitis and the gallbladder,” said Marino. “CVS is kind of similar [to CHS], but people aren’t using cannabis.” So asking about marijuana use history can clearly help.

“The main thing seems to be people who use heavily and regularly: daily use or near-daily use,” said Marino. “With the rise of medical cannabis, more people have access to it, so maybe there are more presentations now than there used to be. But with no ICD [International Classification of Diseases] code, I don’t think you’d be able to say whether you can find prevalence.”

Marino acknowledges that there’s a fine line to tread in questioning patients, especially in situations where they are worried about law enforcement, and some healthcare providers are better than others at getting honest histories. “There are going to be people on the provide side who don’t get the truth out of patients, and there are patients who won’t disclose. This is why the way we treat patients is important.”

Gastroenterologists’ Perspectives

 Whether they’re called in to consult in the emergency department or see a person in their office, gastroenterologists have a big role to play for CHS patients. CHS has been known about since 2004, but a seminal 2011 Current Drug Abuse Reviews article put gastroenterologists on the alert.

A year ago, Healio interviewed gastroenterologist Joseph Habboushe, MD for an article titled “Cannabinoid hyperemesis syndrome: What GIs should know.” Habboushe had surveyed 155 patients in an emergency department who reported smoking marijuana frequently and found that 32.9 percent of them met criteria for CHS. He concluded that the syndrome is vastly underreported.

“I would definitely ask” about marijuana use in the case of an otherwise-healthy, vomiting patient, said Lisa Gangarosa MD, AGAF, FACP, professor of Medicine at the UNC Division of Gastroenterology and Hepatology, speaking for the American Gastroenterological Association. “The diagnosis is largely made on the history.”

There is no clear test. “Basically, if the history fits, and if the patient stops smoking and gets better, that’s what it was.”

Some testing would be done to exclude other problems, such as stomach cancer, a large ulcer or gallstones, Gangarosa told Filter. It’s also important to conduct basic lab testing, such as for pregnancy, and then, if all of that testing comes back negative, to think about endoscopy and ultrasound of the gallbladder.

Gangarosa has only seen CHS in patients who have been “smoking pot,” not in anyone who has been prescribed dronabinol, which is synthetic THC.

There is no clear test for the syndrome. “In some cases you can say your impression is suspected marijuana-induced hyperemesis,” she said. “Basically, if the history fits, and if the patient stops smoking and gets better, that’s what it was.”

Surprisingly, many patients who use cannabis haven’t heard of CHS, said Gangarosa. For others, they don’t want to stop smoking, “and they don’t want to believe that this is the cause of their problems. It’s the same thing with pancreatitis—just because of the health harms, doesn’t mean people want to give up drinking.”

The Hot Bath Phenomenon

Andrew Meltzer, the ED physician, said that some of his patients have taken six-to-eight warm baths a day to relieve symptoms.

This reminds me of a personal experience. A member of my family had acute gastritis at the age of six, with a lot of vomiting, and was hospitalized for a week. All she wanted to do was lie in the hospital bathtub with the water as hot as possible. There was no marijuana involved, but bells went off in my head when I heard about the hot shower “cure.” Could this be a common way of responding to extreme vomiting and pain in general?

Experts stress that the hot shower treatment is anecdotal, and can’t be used as a sure sign of CHS. “But it’s something I ask people,” said Ryan Marino. “It seems as if most people have figured out” that it works. “It might be that they’re so symptomatic they try anything, and find the one thing that works.”

Like the capsaicin, which provides heat, and heating pads, heat from the hot shower on the belly might relieve the pain, said Marino. However, “I don’t think anyone has a good reason for the link” between CHS and hot showers.

A Researcher’s View

The National Institute on Drug Abuse (NIDA) referred Filter to Kiran Vemuri, PhD, a research assistant professor at Northeastern University in Boston, who has a grant from the agency to find an antidote for synthetic cannabinoid intoxication.

That, of course, is a very different issue from CHS. But as an organic chemist, Vemuri has studied emesis from a CB1 antagonist perspective. He is aware of the paradox with THC: The synthetic version, dronabinol, is approved by the FDA to treat the nausea and vomiting associated with chemotherapy, as well as to increase appetite in wasting associated with AIDS, and for many other conditions.

How would the same substance that treats nausea induce it?

“This only happens in people who have been consuming cannabis for a long time,” Vemuri said. But he noted that most information in the literature is anecdotal and based on case histories. “People try to come up with a number”— how much cannabis, for how long—“but you can never really tell as to what causes the hyperemesis. Is it the dose, is it the strain?”

“If you know the CB1 receptor is implicated … the best treatment option would be an antagonist.” Except there isn’t one.

Vemuri has studied antagonists which induce nausea, with the CB1 receptor the biological target. CB1 receptors are all over the body, but most are in the brain, he said.

If you want to know everything the top researcher in emesis (vomiting) knows about the topic, look up the work of Linda Parker. It’s hard to study in animals, because not all of them even vomit.

There is no antidote for emesis itself, said Vemuri. “But if you know that the CB1 receptor is implicated, and the patient is presenting with an overdose of THC or synthetic cannabinoids, the best treatment option would be an antagonist.” Except there isn’t one.

As for the hot showers, CB1 receptors could indeed be involved, but there is no “concrete connection” to CHS or its treatment, said Vemuri.

And he cautions that “‘overdose’ is a big word when it comes to THC.” The dose, the strain, the route of administration all matter, he said. And because THC can reside in fat, and build up, it makes sense that some of the side effects could be worse in people who have consumed THC over a long period of time. “At the end of the day, anything in excess is not good.”  

No Easy Cure

There was one medication which briefly showed promise for CHS—ribonabant—but it was removed from the market due to psychiatric side effects (suicidal ideation). “The target is so new,” Vemuri said. “But NIDA is definitely interested, and no one ever gave up on the target, and no one ever gave up on cannabis, and no one ever gave up on the antagonists. Recently I was at a conference where I got to know companies that are pursuing both CB1 and CB2.”

While hot showers may provide temporary relief, and anti-emetics and intravenous hydration can help “someone in the throes of repetitive vomiting,” for now, the best way for CHS patients to avoid further symptoms for good is to stop using cannabis, said Lisa Gangarosa, the gastroenterologist.

“That is always the recommendation,” agreed Marino. “It seems to be the only thing that makes it better or makes it go away. But it’s not always the easiest thing. It’s easy for me to say.”

The implications of quitting for people who use cannabis for medical reasons—and the difficulties for people who are addicted—are clear. But for now, the unknown minority of cannabis users unfortunate enough to experience cannabis hyperemesis syndrome have no other reliable recourse.

Source:  https://www.dbrecoveryresources.com/2019/04/what-is-cannabis-hyperemesis-syndrome/ April 2019

The doctors told Regina Denney and her son Brian Smith Jr. what was causing his severe vomiting and abdominal pain.

Neither the teenager nor his mother believed what they said: smoking weed.

Smoking marijuana, the two knew, was recommended to cancer patients to spur the appetite. How could it lead to Brian’s condition?

As the months went by and the pounds slipped off Brian’s once healthy frame, it was clear that whatever was causing his stomach troubles had just the opposite effect.

Brian kept smoking. The symptoms continued on and off.

Last October, after another severe bout of vomiting, the teenager died. He was 17 years old.

Five months later, as Denney pored over a coroner’s report for answers, she finally accepted that marijuana played a pivotal role in her son’s death. The autopsy report, which Denney received in March, attributed her son’s death to dehydration due to cannabinoid hyperemesis syndrome.

“We had never heard about this, had never heard about marijuana causing any vomiting. He and I were like, ‘Yeah, I think it’s something else,’ ” Denney said. “Brian did not believe that was what it was because of everything we had ever been told about marijuana. … It didn’t make any sense.”

Cannabinoid hyperemesis syndrome, also known as CHS, can arise in response to long-term cannabis use. The syndrome consists of vomiting, nausea and abdominal pain, which can often be alleviated by taking hot showers.

Doctors say CHS is on the rise, but they are not certain why. Marijuana is more available than in years past, and it is more potent.

Rarely does CHS result in death.

‘Basically, they smoked weed’

Denney didn’t like the fact that her teen son started smoking at 13, but she figured the situation could be worse. Brian and she had a strong relationship, and he always had been honest with her about his use of marijuana.

For the most part, Brian was a good kid who had a tightknit group of friends who called themselves the GBS, Gimber Block Savages, after the south side street where many of them lived. Although they called themselves a gang, Denney said, they never caused any trouble.

“Basically, they smoked weed,” she said.

About two years after Brian started smoking, he began using a lot more, perhaps to help deal with depression, Denney said. He dropped out of school after ninth grade and started working full-time with an uncle who had a tree-trimming business. Brian helped clear brush.

The job provided enough money to support his marijuana habit, another reason Denney felt there was no reason for her to intervene. After all, many of Brian’s peers were using heroin or methamphetamine.

“I thought, ‘OK, if that’s all he’s doing, smoking marijuana, pick and choose your battles,’ ” she said. “If this is the worst thing he’s doing, I’m OK. He’s not in any trouble legally. He’s not playing with guns, robbing people and stealing things. He’s supporting his own habit. I thought, ‘OK, this is what it is.’ ”

Denney had no reason to be concerned about cannabinoid hyperemesis syndrome. She, like many others, had never heard of it.

‘A totally underdiagnosed entity’

A few years ago, many doctors had no idea this condition existed. First described 15 years ago, CHS symptoms follow heavy cannabis use and include intense stomach pain, bouts of vomiting and debilitating nausea.

A study published last year in the journal Basic & Clinical Pharmacology & Toxicology surveyed urban emergency room patients who smoked marijuana 20 or more days a month. Of the 155 who said yes, almost a third experienced CHS symptoms.

Source: Indiana boy, 17, died from smoking weed. CHS is to blame. What is CHS? (usatoday.com) September 2019

30 July 2019

I had forgotten how much I disliked cannabis until I found myself under its influence, in the rain, trying and failing to find Toronto’s Union Train Station so I could get to the airport and go home. The plan had been to enhance my mood for a long journey, floating back to the UK in a higher state of consciousness. In practice, I just got confused, wet and was lucky to make my flight.

I had intended to purchase the kind of low-THC, high-CBD weed that disappeared from Britain’s black market when skunk took over in the 1990s. Put simply, THC is the psychoactive component that gets you high but is associated with psychosis, while CBD is the antipsychotic component that gave cannabis its natural balance before it was bred out of the plant by drug dealers. Alas, laziness prevailed and I settled for a ready-rolled joint which my vendor candidly admitted was made up of scrapings from whatever they’d been chopping up that day.

In truth, the spliff had been bought on the ‘when in Rome’ principle. Recreational cannabis has been legal in Canada since last October and I was on a fact-finding trip with a BBC film crew and a cross-party group of MPs, including Norman Lamb, David Lammy and Jonathan Djanogly. In a few months time, Illinois will become the eleventh US state to legalise recreational marijuana. With the dominos falling, it is only a matter of time before a European country, possibly Britain, follows suit. We were there to see how it works.

Only two of us sampled the product. Norman Lamb received a knighthood for his work on mental health while we were there and marked the occasion by becoming the first British politician to be filmed buying and taking cannabis. I wish I could claim that it was a wild party, but the truth is more mundane. Struggling with jet lag and keen to get a decent night’s sleep, he tried a little cannabis oil. I am told the results were satisfactory.

Being male, middle-aged and more or less law-abiding, Sir Norman and I are demographically just the kind of chaps to dabble in the legal marijuana market. More people are consuming cannabis in Canada since it was legalised, with prevalence rising from 14 per cent to 18 per cent in the last year. In the first quarter of 2019, 646,000 people, most of them men and half of them aged over 45, tried cannabis for the first time. The most common reason given by these debutants for buying cannabis on the legal market is ‘quality and safety’. It is not so much that the law was an effective deterrent – everybody knew the police barely enforced it – rather that would-be consumers were put off by the idea of buying an unregulated product from a criminal supply chain.

The problem is that there are more than four million Canadians who are used to buying on the black market and have been given little incentive to stop. An illicit cannabis market that was worth $1,289 million in the last full quarter before legalisation was still worth $1,014 million in the first quarter of this year. The legal, recreational market was worth a mere £377 million. The illicit trade is proving hard to shake off.

Everyone I spoke to in Ontario was eager to point out that these are early days. Canada is only the second country to legalise cannabis (after Uruguay) and there were bound to be teething problems. There is a temporary shortage of both cannabis and shops from which to buy it. Toronto, a city of three million souls, has just four recreational cannabis shops. Nevertheless, the primary goal of legalisation was to take out the criminal element and so it is concerning that most of the country’s weed continues to be sourced on the black market.

Things are unlikely to improve until prices fall. The average gram of cannabis on the street costs $6.37. The average gram in a shop costs $9.99. Casual smokers might be prepared to pay ten bucks for government-approved cannabis, but the costs of switching to the legal market start to add up if you’re one of the two million Canadians who consume the drug at least once a week.

Marijuana is being produced on a truly industrial scale in Canada. Factories are turning seeds into six foot plants in a matter of weeks. The legal product could easily be sold cheaper than its illicit competitors, but over-regulation, taxation and a lack of competition have got in the way. Politicians hoped to smash the black market while regulating the product in such a way that it would not attract new punters. These two goals were never easy to reconcile, and neither has been achieved. High prices, plain packaging and restrictive licensing conditions have deterred long-term users from switching to the legal market while new customers have given it a try anyway.

Everything about Toronto’s cannabis shops feels regulated to the last inch. Browsing their shelves gave me a fresh appreciation for the subtle nudges of consumer capitalism. With logos and colours stripped from the packaging, there is nothing to signal quality, economy or potency; nothing to remember. The windows are blacked out. Edible and vaped cannabis cannot be sold. Small quantities of marijuana are held in over-sized plastic tubs, apparently to provide enough room for large yellow warning labels. The only concession to branding is that some of the tubs are white and some are black.

It all amounts to a concerted effort to suck the fun out of cannabis shopping, which makes sense if your aim is to deter people from buying the stuff, but not if your aim is to switch people from street cannabis to high street cannabis.

On an Indian reservation outside Toronto things could not be more different. Here, in a settlement of 4,100 people, there are no fewer than nineteen cannabis shops. Although it is illegal for visitors to take their shopping off-site, the authorities turn a blind eye to it as part of their efforts to atone for historic wrongs done to the indigenous population. As far as the proprietors are concerned, the unique selling point is their organic, homegrown product which they have reverse-engineered into the Indian way of life, but the real difference between these shops and their state-sanctioned counterparts is variety, low prices and an unabashed pride in selling something that is pleasurable.

All the weed sold here is unlicensed and therefore technically illicit, but when we visited, eight months after federal legalisation, it was doing good business. Until the Canadian government loosens up and allows a little more consumerism into its noble experiment, neither they nor the rest of the unlicensed sector have much to fear.

Source: Christopher Snowdon Spectator Magazine July 2019

Colorado is on the front lines in dealing with how marijuana use affects surgery. Lessons learned on operating tables and in recovery rooms have prompted calls for more research on marijuana nationwide.

DENVER — When Colorado legalized marijuana, it became a pioneer in creating new policies to deal with the drug.

Now the state’s surgeons, nurses and anesthesiologists are becoming pioneers of a different sort in understanding what weed may do to patients who go under the knife.

Their observations and initial research show that marijuana use may affect patients’ responses to anesthesia on the operating table — and, depending on the patient’s history of using the drug, either help or hinder their symptoms afterward in the recovery room.

Colorado makes for an interesting laboratory. Since the state legalized marijuana for medicine in 2000 and allowed for its recreational sale in 2014, more Coloradans are using it — and they may also be more willing to tell their doctors about it.

Roughly 17% of Coloradans said they used marijuana in the previous 30 days in 2017, according to the National Survey on Drug Use and Health, more than double the 8% who reported doing so in 2006. By comparison, just 9% of U.S. residents said they used marijuana in 2017.

“It has been destigmatized here in Colorado,” said Dr. Andrew Monte, an associate professor of emergency medicine and medical toxicology at the University of Colorado School of Medicine and UCHealth. “We’re ahead of the game in terms of our ability to talk to patients about it. We’re also ahead of the game in identifying complications associated with use.”

One small study of Colorado patients published in May found marijuana users required more than triple the amount of one common sedation medicine, propofol, as did nonusers.

Those findings and anecdotal reports are prompting additional questions from the study’s author, Dr. Mark Twardowski, and others in the state’s medical field: If pot users indeed need more anesthesia, are there increased risks for breathing problems during minor procedures? Are there higher costs with the use of more medication, if a second or third bottle of anesthesia must be routinely opened? And what does regular cannabis use mean for recovery post-surgery?

But much is still unknown about marijuana’s impact on patients because it remains illegal on the federal level, making studies difficult to fund or undertake.

It’s even difficult to quantify how many of the estimated 800,000 to 1 million anesthesia procedures that are performed in Colorado each year involve marijuana users, according to Dr. Joy Hawkins, a professor of anesthesiology at the University of Colorado School of Medicine and president of the Colorado Society of Anesthesiologists. The Colorado Hospital Association said it doesn’t track anesthesia needs or costs specific to marijuana users.

As more states legalize cannabis to varying degrees, discussions about the drug are happening elsewhere, too. On a national level, the American Association of Nurse Anesthetists recently updated its clinical guidelines to highlight potential risks for and needs of marijuana users. American Society of Anesthesiologists spokeswoman Theresa Hill said that the use of marijuana in managing pain is a topic under discussion but that more research is needed. This year, it endorsed a federal bill calling for fewer regulatory barriers on marijuana research.

Why Should Patients Disclose Marijuana Use? 

No matter where patients live, though, many nurses and doctors from around the country agree: Patients should disclose marijuana use before any surgery or procedure. Linda Stone, a certified registered nurse anesthetist in Raleigh, N.C., acknowledged that patients in states where marijuana is illegal might be more hesitant.

“We really don’t want patients to feel like there’s stigma. They really do need to divulge that information,” Stone said. “We are just trying to make sure that we provide the safest care.”

In Colorado, Hawkins said, anesthesiologists have noticed that patients who use marijuana are more tolerant of some common anesthesia drugs, such as propofol, which helps people fall asleep during general anesthesia or stay relaxed during conscious “twilight” sedation. But higher doses can increase potentially serious side effects such as low blood pressure and depressed heart function.

Limited airway flow is another issue for people who smoke marijuana. “It acts very much like cigarettes, so it makes your airway irritated,” she said.

To be sure, anesthesia must be adjusted to accommodate patients of all sorts, apart from cannabis use. Anesthesiologists are prepared to adapt and make procedures safe for all patients, Hawkins said. And in some emergency surgeries, patients might not be in a position to disclose their cannabis use ahead of time.

Even when they do, a big challenge for medical professionals is gauging the amounts of marijuana consumed, as the potency varies widely from one joint to the next or when ingested through marijuana edibles. And levels of THC, the chemical with psychoactive effects in marijuana, have been increasing in the past few decades.

“For marijuana, it’s a bit of the Wild West,” Hawkins said. “We just don’t know what’s in these products that they’re using.”

Marijuana’s Effects On Pain After Surgery

Colorado health providers are also observing how marijuana changes patients’ symptoms after they leave the operating suite — particularly relevant amid the ongoing opioid epidemic.

“We’ve been hearing reports about patients using cannabis, instead of opioids, to treat their postoperative pain,” said Dr. Mark Steven Wallace, chair of the pain medicine division in the anesthesiology department at the University of California-San Diego, in a state that also has legalized marijuana. “I have a lot of patients who say they prefer it.”

Matthew Sheahan, 25, of Denver, said he used marijuana to relieve pain after the removal of his wisdom teeth four years ago. After surgery, he smoked marijuana rather than using the ibuprofen prescribed but didn’t disclose this to his doctor because pot was illegal in Ohio, where he had the procedure. He said his doctor told him his swelling was greatly reduced. “I didn’t experience the pain that I thought I would,” Sheahan said.

In a study underway, Wallace is working with patients who’ve recently had surgery for joint replacement to see whether marijuana can be used to treat pain and reduce the need for opioids.

But this may be a Catch-22 for regular marijuana users. They reported feeling greater pain and consumed more opioids in the hospital after vehicle crash injuries compared with nonusers, according to a study published last year in the journal Patient Safety in Surgery.

“The hypothesis is that chronic marijuana users develop a tolerance to pain medications, and since they do not receive marijuana while in the hospital, they require a higher replacement dose of opioids,” said Dr. David Bar-Or, who directs trauma research at Swedish Medical Center in Englewood, Colo., and several other hospitals in Colorado, Texas, Missouri and Kansas. He is studying a synthetic form of THC called dronabinol as a potential substitute for opioids in the hospital.

Again, much more research is needed.

“We know very little about marijuana because we’ve not been allowed to study it in the way we study any other drug,” Hawkins said. “We’re all wishing we had a little more data to rely on.”

Source: If You Smoke Pot, Your Anesthesiologist Needs To Know – KFF Health News August 2019

INTRODUCTION

In 2013, Uruguay became the first country in fully regulating the marijuana market that now operates under state control.

In a Washington Post feature article on Uruguay’s cannabis laws, they reported that Uruguay is socially liberal and has a wide separation of church and state. Gambling and prostitution are legal and regulated. Uruguay is also the only Latin American nation outside Cuba that has broadly legalised abortion, and it was one of the first to recognize civil unions and adoption by same-sex couples. Uruguay also is accustomed to relatively high levels of regulation and a big state role in the economy, with an array of government-owned banks, gas stations and utilities. Over the years, activists began to argue: Why not weed?

As early as 1974, Uruguay decriminalised possession of “a minimum quantity [of illicit substances], intended solely for personal use.” Exactly what constituted a “minimum quantity” was never clarified, giving judges broad discretion in its interpretation.

The initiative of marijuana regulation was by the then president José Mujica. Lawmakers in Uruguay (population: 3.3m) signed the country’s cannabis bill into law in December 2013 and pharmacies began selling two strains of legal marijuana cultivated by two government-authorised firms in July 2017.

The text of the law expresses its goals through three main objectives, which included reducing drug trafficking-related violence by taking cannabis off the black market, and promoting public health through education and prevention campaigns, thereby “minimising the risks and reducing the harm of cannabis use”.

Uruguay was the first country to leave behind the global ban on non-medical cannabis that began with the United Nations’ 1961 Single Convention on Narcotic Drugs, and despite repeated criticisms from the International Narcotics Control Board (INCB), as in the Board’s report for 2016, which states:

The Board notes the continued implementation by the Government of Uruguay of measures aimed at creating a regulated market for the non-medical use of cannabis… [T]he Board wishes to reiterate its position that such legislation is contrary to the provisions of the international drug control conventions… according to which States parties are obliged to ‘limit exclusively to medical and scientific purposes the production, manufacture, export, import, distribution of, trade in, use and possession of drugs.’

Concerned that their policy would come under intense scrutiny from their neighbours and from the broader international community, Uruguayan authorities deliberately opted for a strict approach to regulation, such as a user registry and monthly sales limits.

In an attempt to reassure the international public opinion, President José Mujica, said that his government would not allow unlimited use of marijuana and illicit drug dealing: “And if somebody buys 20 marijuana cigarettes, he will have to smoke them. He won’t be able to sell them“.

And in order to convince the majority of the Uruguayan population, the President Mujica promised to launch at the same time “a campaign aimed at young people on how to consume marijuana. Avoid, for example, to smoke to not damage the lungs but inhale or consume it with food“.

In response to public opposition, the Open Society Foundation headed by the financier George Soros announced the launch of a massive media campaign across the nation to manipulate the public consensus. Time magazine (5 Aug 2013) reported that “a massive media campaign, with television ads funded partly by Soros’ Open Society Foundations group, were required to convince opponents of legalisation”.

STATE CONTROL – HOW IT WORKS

There are three ways to legally obtain cannabis in Uruguay. The first alternative is autocultivo, which allows individuals to grow up to six marijuana plants per household and yield an annual crop of 480 grams per year, or 40 grams per month. All individuals must register with the government agency for the regulation and control of cannabis—called the Instituto de Regulación y Control de Cannabis (Cannabis Regulation and Control Institute) to grow these plants in their home and no person may register more than one location for domestic growth. The second alternative is the Cannabis Club, which allows between 15 to 45 members of a duly-registered civil association to farm up to 99 marijuana plants in specific locations. Each club may not supply any individual with more than 480 grams of marijuana per year. The third alternative is sale through pharmacies. This alternative will allow a registered consumer to buy up to 40 grams of marijuana per month and 480 per year in person from pharmacies that are registered with the IRCCA and the Ministry of Public Health. On July 19, 2017, Uruguay launched the last remaining stage of the cannabis law, with sales finally beginning in 16 pharmacies across the country.

PUBLIC DISAPPROVAL

Public opinion surveys have consistently shown most Uruguayans to be doubtful about the government’s initiative.

According to the results of the 2014 AmericasBarometer survey in Uruguay, only 34% of Uruguayans approved the new regulations regarding the liberalization of marijuana use, while 60.7% showed their disapproval to the new policies. Perhaps not surprisingly, approval for the new regulation of cannabis is closely related to previous personal experimentation with marijuana and a history of marijuana consumption among relatives and close friends.

PUBLIC SKEPTICISM

As of 2014, most Uruguayans remained skeptical about the benefits the new regulation will bring. For instance, 42% of Uruguayans considered that the general situation of the country would worsen as a result of regulation, while only 19% believed that the situation would improve. Among the most negative opinions expressed, 70% of Uruguayans stated that public safety and public health conditions would either worsen or remain the same. The issue that seemed to generate the most positive opinions was related to the fight against drug trafficking organisations.

Source: https://www.vanderbilt.edu/lapop/insights/ITB020en.pdf

PUBLIC USAGE

In 2001, 5.3% of the population admitted to having consumed marijuana.

By 2014, life prevalence had quadrupled with 22.1% of Uruguayans acknowledging some consumption.

Since Uruguay legalised the sale of marijuana, underage use increased from 14% to 21%. Use by those aged 19 to 24 increased from 23% to 36% Those aged 25 to 34 increased from 15% to 25%.

Source: https://wdr.unodc.org/wdr2019/prelaunch/WDR19_Booklet_5_CANNABIS_HALLUCINOGENS.pdf

TEENS

Prevalence doubled among secondary school students from 2003 to 2014. In 2003, 8.4% of students had consumed marijuana during the previous twelve months. in 2014, 17% had.

Almost a quarter of the high-frequency users of Montevideo had their first experience with marijuana before age turning 15 (24.1%).

Prevalence is also higher among 18-25 year-olds than other age categories.

NON-COMPLIANCE

As at February 2018, 8,125 individuals and 78 cannabis clubs with a total of 2,049 members were registered in addition to the 20,900 people registered through pharmacy sales for cannabis. The system potentially provides cannabis to around 30,000 of the 140,000 past-month cannabis users estimated in Uruguay in 2014.

A recent survey found that almost 40% said they would probably or definitely flout the law which requires registration. (19.6% state that it is not probable that they will register, and another 19.6% said that they are certain that they will not register.)

MONITORING AND EVALUATION

A 2018 Brookings Institute report details how the Ministerio de Salud Pública is required to submit an annual report on the impacts of the legalization since 2014 – but the ministry has only submitted such a report once, in 2016, and the findings were not made public.

According to a report by WOLA (funded by Open Society Foundations – aka George Soros) and posted on the Monitor Cannabis Uruguay site, in spite of President Vázquez’s support for monitoring and evaluation, his administration has provided the public with relatively little in the way of hard data on the early effects of initial implementation of the cannabis measure.

The IRCCA’s limited staff – it has a team of six inspectors who are responsible for ensuring compliance – does not realistically allow the institute to check the annual plant yields for all 8,000+ homegrowers and approximately 80 registered clubs.

 PRODUCTS

A recent study of marijuana consumers in Montevideo found that users had consumed it in several different ways during the past year, including vaporizers (15.7%), edibles, such as brownies, cakes, cookies (26.4%), and drinks, such as mate, milkshakes, daiquiris (9.4%).

PERCEPTION OF RISK

The study of marijuana consumers in Montevideo also found that users had a very low perception of risk associated with undertaking several activities while under the influence of marijuana. For instance: 21.4% of respondents drove a car under the influence of marijuana; 28.4% rode a motorcycle; 11.2% operated heavy equipment. More than half of the respondents (55.4%) declared that they consumed marijuana and went to work before four hours had passed.

More than one in every four of those women who were pregnant (26.1%) reported to having continued consuming marijuana while pregnant.

BLACK MARKET

Three years after legalisation, seven out of every ten cannabis consumers still acquire the product on the black market. Authorities admit that “street selling points have multiplied in recent years, along with criminal acts related to micro trafficking.”

Marcos Baudeán, a member of the study group Monitor Cannabis Uruguay, suggests it may be worse than that: “Consider the fact that there are 55,000 regular consumers who are responsible for 80% of the marijuana consumption in the country, but currently only 10% are consuming from the legal market, the rest are buying the drug off the illegal market.”

Others have pointed to the very low concentration of THC in the legal drug as another reason why some users may turn to the black market. Though the price may be higher — a gram of high-potency illegal marijuana can cost as much as $20— some users may be willing to pay this premium in exchange for access to a more powerful drug.

Because sales to tourists are prohibited, some Uruguayan homegrowers and clubs have attempted to get around the ban by offering ‘cannabis tours’, which are framed more as social and educational experiences, in which participants are free to sample cannabis while on a paid tour. Others simply sell directly to tourists behind closed doors, a grey market quietly operating via word of mouth.

FINANCIAL IMPLICATIONS

An unexpected consequence of Uruguay’s marijuana law is that the U.S. government invoked the Patriot Act which prohibits U.S. banks from handling funds for distributors of marijuana.  In Uruguay, this is by way of the pharmacies only.  International banks – both those with U.S. headquarters such as Citibank and European banks such as Santander have advised their Uruguayan branches that they are prohibited from providing services to the distributors of marijuana.

As a result, pharmacies tasked with the sale and distribution of marijuana have been cut off from the entire financial services market because the banks in Uruguay announced that every business associated with the newly legal marijuana industry risked being in violation of the U.S. drug laws and would lose their access to U.S. banks and dollar transactions.

SUMMARY

What we have learned from the data so far indicates that frequency of consumption has significantly increased, especially in the 15-24 age group. The perception of risk with drug use is low, and risky behaviours have increased with the frequency of consumption, including use of marijuana during pregnancy. The black market is alive and well. And the overwhelming support for the regulation among high-frequency marijuana users does not immediately translate into willingness to comply with it. Of most concern is that monitoring and reporting of the effects of legalisation is minimal, and not made public.

The drug-friendly website CannabisWire in July 2018 summed it up perfectly. “What Have We Learned From the First Nation to Legalize Cannabis? Not Enough.”

Source: Uruguay – Say Nope to Dope 2019

Source: Time to Hit Pause on Marijuana Legalization – InsideSources July 2019

Abstract:

Background: The relationship between cannabis and violence remains unclear, especially amid those with severe mental illnesses (SMI). The objective of this meta-analysis was to investigate the cannabis-violence association in a population of individuals with a SMI.

Method: A systematic search of literature using PubMed, PsychINFO, Web of Science and Google scholar was performed (any time-August 2018). All peer-reviewed publications assessing both cannabis use and the perpetration of violence in an SMI sample were included. Data on several key study characteristics such as the proportion of SMI in the sample as well as the number of cannabis users and violent participants were extracted. Odds ratios (OR) were likewise extracted and aggregated with random-effects models.

Results: Of the potential 2449 articles that were screened for eligibility, 12 studies were analyzed using a random-effect meta-analysis. Results showed a moderate association between cannabis use and violence (OR = 3.02, CI = 2.01–4.54, p = 0.0001). The association was significantly higher when comparing cannabis misuse (OR = 5.8, CI = 3.27–10.28, p = 0.0001) to cannabis use (OR = 2.04, CI = 1.36–3.05, p = 0.001).

Conclusion: These findings are clinically relevant for violence prevention/management and highlight the necessity of further investigations with methodologically-sound studies. Thus, longitudinal studies adjusting for important confounding factors (i.e., psychopathic traits and stimulant use) are warranted

Source: Cannabis use and violence in patients with severe mental illnesses: A meta-analytical investigation – PubMed (nih.gov) April 2019

In March 2014, the Colorado Department of Public Health and Environment (CDPHE) learned of the death of a man aged 19 years after consuming an edible marijuana product. CDPHE reviewed autopsy and police reports to assess factors associated with his death and to guide prevention efforts.

The decedent’s friend, aged 23 years, had purchased marijuana cookies and provided one to the decedent. A police report indicated that initially the decedent ate only a single piece of his cookie, as directed by the sales clerk. Approximately 30-60 minutes later, not feeling any effects, he consumed the remainder of the cookie.

 During the next 2 hours, he reportedly exhibited erratic speech and hostile behaviors. Approximately 3.5 hours after initial ingestion, and 2.5 hours after consuming the remainder of the cookie, he jumped off a fourth floor balcony and died from trauma.

The autopsy, performed 29 hours after time of death, found marijuana intoxication as a chief contributing factor. Quantitative toxicologic analyses for drugs of abuse, synthetic cannabinoid, and cathinones (“bath salts”) were performed on chest cavity blood by gas chromatography and mass spectrometry. The only confirmed findings were cannabinoids (7.2 ng/mL delta-9 tetrahydrocannabinol [THC] and 49 ng/mL delta-9 carboxy-THC, an inactive marijuana metabolite). The legal whole blood limit of delta-9 THC for driving a vehicle in Colorado is 5.0 ng/mL. This was the first reported death in Colorado linked to marijuana consumption without evidence of polysubstance use since the state approved recreational use of marijuana in 2012.

Source:  MMWR Morb Mortal Wkly Rep. 2015 Jul 24;64(28):771-2.

Abstract
Cannabis has been shown to be teratogenic in cells, animals and humans. Particular targets of prenatal exposure include brain, heart and blood vessels and chromosomal segregation. Three longitudinal clinical studies report concerning cortical dysfunction persisting into adolescence and beyond, which are pertinent to the autism epidemic.
Increased rates of congenital heart defects, gastroschisis, anencephaly and others have been reported. The pattern of neuroteratology seen after cannabis exposure strongly suggests a spectrum of dysfunction from mild to moderate to very severe. Downs syndrome, atrial septal defect (secundum type), ventricular septal defect and anotia / microtia were noted to be more common in prenatally cannabis exposed children in a large US epidemiological study which would appear to have been confirmed by recent experience in Colorado and other USA states.

Studies in cells, together with the above mentioned epidemiology, implicate cannabidiol, cannabichromene, cannabidivarin and other
cannabinoids in significant genotoxicity and / or epigenotoxicity. Notch signalling has recently been shown to be altered by cannabinoids, which is highly pertinent to morphogenesis of the neuraxis and cardiovasculature, and also to congenital and inheritable cancer induction. It is felt that subtle neurobehavioural psychosocial and educational deficits will likely be the most common expression of cannabinoid teratology at the population level. The far reaching implications of this wide spectrum of neuroteratological, pediatric cardiological and other defects and deficits should be carefully considered in increasingly liberal paradigms. Hence it is shown that the disparate presentations of cannabis teratology relate directly and closely to the distribution of CB1R’s across the developing embryo and account for the polymorphous clinical presentations.

Introduction
At a time when up to 24% of Californian teenage mothers test positive for cannabis, it is of concern that the complex literature relating to the teratology of cannabis seems to have created mixed messages in both professional and popular fora, leading the teratogenic effects of cannabis to be overlooked and the impact of increasing cannabis consumption to be underestimated. It is therefore important to reiterate that a number of independent and well-designed studies have similarly indicated major teratogenic effects associated with both maternal and paternal cannabis use.
In reviewing the teratology of prenatal cannabis exposure (PCE) this paper will concisely consider neurobehavioural effects cardiovascular effects including gastroschisis (which is thought to have a vascular aetiopathology), immune effects, chromosomal effects, genetic and epigenetic effects, mitochondrial effects, the effects of the various different exogenous cannabinoids, and notch signalling.

Source: Explaining Contemporary Patterns of Cannabis Teratology (dalgarnoinstitute.org.au) January 2019

IS the Home Office really supporting a scheme which will allow drug users to get their illegal class A drugs tested for ‘purity and quality’ without fear of prosecution? 

Is Sajid Javid really stupid enough to back this idea? The naive justification is that it will reduce ‘overall harm’. While it will not, it will certainly become a licence for addiction and for normalising intrinsically harmful and destructive class A drug use.

Pity the poor children of such drug-users who, on top of putting their habit above their family’s needs and wellbeing, will now be able to take into their homes drugs which they can claim the government has deemed safe.

Such a process gives the misleading impression that that it is only any impurities in these toxic substances that can cause harm. As if impurities in the drugs were the top of drug addicts’ list of concerns; or as if you could take any drug with impunity providing it had been tested and declared pure.

Hello, Sajid! Wake up! I think you are being taken for a ride! Why else is diamorphine so carefully controlled and prescribed? Maybe despite being Home Secretary perhaps you’ve not visited any rehabs or talked to former addicts. They’d put you straight pretty quickly.

Have you not in your time in government visited enough drug ridden estates to know that it is drug use that is the problem that corrupts and endangers families and young people’s lives?

Have you not seen cocaine burn-out amongst your former City colleagues? Have you not seen the fall-off of any moral sense in the lives of those for whom their drug use inevitably becomes paramount, at the expense of everything and everyone else?

In case it has escaped your notice, there is a sustained campaign going on driven by middle-class libertarians to chip away at drug controls and to legalise drug use. It may well suit their selfish sensibilities to be free to do what they like but it is a disaster for those with fewer choices, fewer buffers and more vulnerability. That includes fatherless families, the poor and children, particularly children in care.

We’ve seen it in the campaign, coming from the heart of the establishment, to allow onsite drug-testing at festivals, driven by Dr Fiona Measham, a member of the Government’s Advisory Council on the Misuse of Drugs. Never mind that such experiments cannot but encourage and pressurise immature young people to use drugs for the first time. They are safe and legal – hey, you can’t say no!

The elites who are pushing this, just like the elites – headed currently by Crispin Blunt MP  – pushing to legalise cannabis are blind to the harm it wreaks on vulnerable communities. This is what police officer Richard Cooke confirms in the Telegraph, and he is right: cannabis does have a pernicious influence on society. Users are disproportionately found among the underprivileged, criminals and the mentally ill. The consequential knock-on effects do stoke violence both in the home and on the streets.

Yet the last year or so has seen increasingly well-funded and pretty much nonstop attempts to erode our drug laws, from decriminalising or legalising cannabis to the recent costly and non-effective heroin prescription plan. 

And going along with the libertarian Mr Blunt (who last year set up a lobbying firm funded by overseas cannabis corporations) and the well heeled drug advocates of his All Party Parliamentary Group on Drug Policy Reform are too many liberalising Chief Constables and Police and Crime Commissioners, no longer up for their real task, which is to crack down on crime, and who see legalisation as the easy route out.

This is the sustained pressure that Sajid Javid appears to be capitulating to, as he did before under pressure from the so-called ‘medicinal cannabis’ lobby, only to have both Dame Sally Davis, the Chief Medical Officer retract and Simon Stevens, head of the NHS, warn that we are making a big mistake with it.

If Mr Javid lets his subversive civil servants and lobbyists at the Home Office and in Parliament push him into licensed testing of illegal class A drugs, he’ll be making another; the country is going to be in very serious long-term trouble. It is not so much a slippery slope as the runaway rapids we’ll find we are heading down.

Source:  https://www.conservativewoman.co.uk/wake-up-home-secretary-this-drug-scheme-is-a-recipe-for-chaos/    June 2019

(Image Credit: 7raysmarketing via Pixabay)

Contrary to advocates’ promises, legalizing pot has spurred new illegal enterprises. https://t.co/1k9twTCrmg via @cjstevempic.twitter.com/VKND92hjl5

— City Journal (@CityJournal) June 12, 2019

Unintended consequences of legislation are more commonplace than they should be, but minimizing them would require more nuanced political debate and that option has probably left us forever.

A new article in City Journal details just how legal marijuana is the gateway drug to illegal marijuana enterprises:

Though advocates claim that one of the benefits of  legalizing recreational marijuana is that the black market will disappear and thus end the destructive war on drugs, the opposite is happening. States that have legalized pot have some of the most thriving black markets, creating new headaches for law enforcement and prompting some legalization advocates to call for a crackdown—in effect, a new war on drugs.

Unlicensed pot businesses have already become a problem for Los Angeles just a year and a half after legalization. The city is devoting police resources that are already stretched thin to address the situation.

City Journal notes that it’s not just mom and pop scofflaws that are problematic:

Legal-pot states are attracting international criminal cartels. Mexican drug gangs have smuggled illegals into Colorado to set up growing operations, former U.S. prosecutor Bob Troyer  wrote last September, explaining why his office was stepping up enforcement. Rather than smuggle pot from Mexico, the cartels grow it in Colorado and smuggle it elsewhere—spurring violence. In 2017, seven homicides in Denver were directly connected to marijuana growers. “I would love to be able to shift some of my resources away from marijuana to other things,” Denver lieutenant Andrew Howard said last year. “But right now, the violence is marijuana or marijuana-related.”

More cartel violence and more illegal immigration…yay legal weed!

I’m no anti-pot Puritan, but I am on record as always having been frustrated by the discussions surrounding legalization efforts. They are rarely in-depth and mostly focus on marijuana’s medicinal uses. It is often portrayed as harmless, which is nonsensical. It’s not heroin, but it’s also not baby aspirin.

What were almost never discussed pre-Colorado were the consequences of legalizing a black market drug. It’s a bit naive to think that the major players from the black market would flee into the shadows once their commodity became legit.

Cartels may be illegal enterprises, but they are still businesses. They can adapt to changing markets. It would appear they are also adept at outreach:

Legal-marijuana businesses are getting in on the game, too. Last year, Denver authorities arrested the owners of a licensed chain of pot shops that employed 350 people for supplying the black market. In January, three owners of the business  pled guilty to drug and racketeering charges. In Oregon, federal prosecutors  arrested six individuals in 2018 and charged them with “vast” interstate-trafficking schemes that supplied black-market pot to Texas, Virginia, and Florida. Some of the suspects were also charged with kidnapping, money-laundering, and use of a firearm in a drug-trafficking crime.

So much for the harmless stoner sales pitch.

None of this is surprising for advocates of smaller government. Legalization and regulation were supposed to make the marijuana black market and its problems go away. Instead, as the City Journal conclusion observes, it’s merely created “Black Market 2.0.”

High times indeed.

Source:  https://pjmedia.com/trending/legal-marijuana-a-boon-to-illegal-cartels/  June 2019

January 3, 2024    |   By Holly Moody-Porter

Source: https://www.umaryland.edu/news/archived-news/december-2023/cannabis-linked-psychiatric-disorders-on-the-rise.php

The title of “Cannabis in Medicine: An Evidence-Based Approach” contains an irony. In chapter after chapter in this multi-authored book written predominately by providers associated with mainstream medical facilities in Colorado, the authors point out the inadequacy of the evidence we have and the absence of the evidence we need to determine how – or even if – cannabis has medical legitimacy. The foreword’s title, “Losing Ground: The Rise of Cannabis Culture,” sets the tone. David Murray, a senior fellow at the Hudson Institute, argues convincingly that “the current experiment with cannabis, underway nationwide [is] leading us towards a future of unanticipated consequences, a future already established in the patterns of use ‘seeded’ in the population but as yet unmanifested.” In other words, the cannabis horse has not only fled the barn but has been breeding prolifically to the point that we couldn’t get rid of it and its progeny if we wanted to!

The 20 chapters following the foreword are divided into basic science (three chapters) and clinical evidence (17 chapters) sections. Over and over in the clinical evidence chapters, individual authors remind the reader of the lack of quality control in production, the dearth of strong evidence from adequately designed research trials, and the intensifying potency of cannabis with attendant dangers, particularly for youth. The organization of this section lacks consistency in that some chapters focus on specialty (e.g. pulmonary medicine), others on patient groups (e.g. the pediatric and adolescent population), others on physiological implications (e.g. clinical cardiovascular effects; neuropsychiatric effects), others on specific diseases (e.g. gastrointestinal disorders; ocular conditions), and still others on public health topics (e.g. cannabis-impaired driving). While all are relevant, a specialty or organ system focus, with a separate public health section might lend the book more coherence. It would also be worth exploring how “cannabis culture” has become in essence a parallel medical system, with many of cannabis’s most ardent proponents as dropouts from establishment medicine after its nostrums for diagnoses like chronic pain, anxiety, and depression have failed to bring them relief.

I would have liked a chapter specifically grappling with the porous boundary between federal and state jurisdictions over cannabis as medicine and marijuana as recreational substance. Lawyer David G. Evans’ admirable chapter on “The Legal Aspects of Marijuana as Medicine” moves in that direction when he writes that, “‘medical marijuana’ is not a ‘states’ rights’ issue.” To wit, for no other drug than cannabis has the federal government ceded regulatory responsibility to states that are variably (but mostly not) equipped to handle it. The truth, complex in its contradictions and inconsistencies, is that in the United States, marijuana remains a Schedule I drug without recognized medical value; the Federal Drug Administration overseeing American pharmaceuticals throws roadblocks in the way of studying it, thereby interfering with the development of a robust evidence base; the federal government has looked the other way and even colluded with the states as one after another has legalized cannabis medically, recreationally, or both; and physicians risk their federal licenses to prescribe if they do more than recommend this drug. In a nutshell, any effort to impose logic is doomed because the American scene vis-à-vis cannabis is seemingly irretrievably illogical.

The editor of this volume, Kenneth Finn, MD, a PMR and pain management specialist in Colorado Springs, Colorado, is to be commended for encouraging individual chapter authors to develop encyclopedic bibliographies. The book can thus serve as a resource for practitioners wishing to delve into a vast and growing literature that continues to offer little that is conclusive. The book can also serve as a primer on what is known about cannabis as medicine, keeping in mind a slant throughout – not necessarily unjustified, at least from an allopathic or osteopathic perspective – that cannabis is neither legitimate as medicine nor safe, even for recreational use.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723137/ Sept-Oct 2020

In the September/October 2020 Missouri Medicine, Polocaro and Vettraino raise the important issue of the transgenerational effects of prenatal cannabinoid exposure (PCE) on subsequent generations.¹ The implications of multigenerational toxicity of cannabinoids is very far-reaching with major policy implications.

The picture presented by Polcaro and Vettraino relating to the mental health implications of PCE is correct if too conservative. As they observe the subject is deeply confounded with multiple other factors impacting post-natal neurological development. For these reasons the significant concordance between reports from five longitudinal studies of childhood development relating to impaired indices of concentration, startle, excitability, poor visuospatial processing and executive functioning including ADHD-like and autism-like features are of particular concern.^2–6 Under a legalization paradigm the state effectively condones unlimited all day every day exposure to extremely high concentrations of THC, other cannabinoids and cannabis tars. What is especially concerning about this is that many of the neurotoxic and neurodevelopmental toxicities of cannabis exhibit threshold dose effects above which severe damage becomes commonplace.⁷ In the context of an increasingly solid consensus relating to the harmful impacts of adult and adolescent cannabis exposure⁸ the implications of PCE-neurotoxicity have not been carefully considered. It has been shown that nationwide autism rates are undergoing an exponential rise and indeed New Jersey has been shown to have 4.5% of 8-year-old boys who carry an autism spectrum disorder diagnosis.^9,10 Our space-time and causal inference studies demonstrate that indeed cannabinoid exposure to THC and cannabigerol amongst other fractions of cannabis, is a principal driver of this nationwide epidemic (manuscript submitted).^9,10

A very concerning consensus is now emerging relating to cannabis-induced teratogenesis, embryotoxicity and fetotoxicity. A 2007 Hawaiian study found that 21 birth defects including many cardiovascular defects, Downs syndrome, orofacial clefts, gastroschisis and arm and hand defects were elevated in offspring of women exposed only to cannabis gestationally with odds ratios up to 40-fold and upper confidence intervals to 123-fold.¹¹ A report on Canada found that total congenital defects were three times more common in the northern territories where cannabis is smoked about three times as much.^12,13 In October 2018 Colorado Health reported an excess of 20,152 total birth defects beyond their baseline expected 67,620 defects 2000–2013 across the period of cannabis legalization when the use of other drugs was falling, representing an elevation of 29.8% above background rates.¹⁴ In a high cannabis use area of Australia 13 defects were found to be elevated compared to Queensland, which for methodological reasons is a conservative estimate.¹⁵ Concerningly elevated rates of Downs syndrome in Colorado, Hawaii, Australia and Canada clearly indicate that heritable cannabis genotoxicity can occur at the hundred megabase chromosomal scale.^11,12,14,15 A close association of atrial septal defect (secundum type) with rising patterns of cannabis use across space and time in the US was recently reported, suggesting that the list of known teratological associations of prenatal cannabis exposure is as yet incomplete.¹⁶ This epidemiological literature is closely concordant with studies in experimental animals.^17–19 Again an abrupt rise in genotoxicity with increasing cannabinoid exposure has been demonstrated for many cannabinoids and is of particular concern.^20–23

Links between cannabis and several paediatric cancers including acute lymphoid leukaemia (ALL), acute myeloid leukaemia, rhabdomyosarcoma and neuroblastoma suggest further implications of cannabinoid genotoxicity.^24–28 Since these tumours together encompass the common tumours of childhood, it is at least possible that cannabis is responsible for the 43% elevation in total childhood cancer across US 1975–2017.²⁹ Indeed Downs syndrome is well known to be associated with a 2,000-fold elevated risk of childhood ALL from 2/100,000 to around 5/100.^30,31

This diverse assemblage of highly congruent evidence of severe cannabis-related neurotoxicity and genotoxicity from varied locations can only be described as extremely concerning indeed. In view of its well described epigenetic and chromoanagenetic effects^32–34 and its clearly transgenerational-multigenerational impacts one can only conclude that if the evidence base is not admitted to the cannabis debate and access to fetotoxic and embryotoxic cannabinoids is not immediately restricted the community will inevitably pay a heinous price in terms of avoidable paediatric neurotoxicity, congenital birth defects, heritable cancerogenesis and multigenerational epigenotoxicity.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721409/ Nov-Dec 2020 in response to ‘Cannabis in Pregnancy and Lactation – A Review’ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723128/

Hemp plants are visible inside several structures on Sept. 16, 2020, in Shiprock, New Mexico.

NOEL LYN SMITH/THE FARMINGTON DAILY TIMES USA TODAY NETWORK – NEW MEXICO

Leaders on the Navajo Nation have cracked down on one of its members who they say has used immigrant labor to transform 400 acres of crop land into hemp farms in the reservation’s northeastern corner.

The crops — illegal under Navajo law — have pitted residents and reservation officials against entrepreneur Dineh Benally, who has formed a partnership with a Las Vegas company that says it develops hemp and cannabis businesses on Native American lands.

Navajo Nation leaders took Benally to court and got an initial victory last week: District of Shiprock Judge Genevieve Woody granted a temporary restraining order halting the hemp farming.

Navajo Nation President Jonathan Nez said the order grants tribal law enforcement officers’ authority to stop hemp production. Navajo Nation police have begun asking some workers on the hemp farms — people law enforcement officials claim are immigrant workers from Asia — to leave tribal land.  

The ruling appears to provide a brief break in the dispute that came to a head this summer over the legality of Benally’s operation, which he claims has also provided employment for more than 200 members of the tribal nation.

The hemp farms are located around Shiprock on the Navajo Nation, which encompasses northeastern Arizona, northwest New Mexico and a sliver of southeastern Utah. 

The farms have prompted protests and allegations that Benally is illegally growing marijuana under the guise of a hemp farm with the help of foreign nationals. 

Both crops are illegal on tribal land. “The hemp will not stay here,” Nez said. 

A few hundred Navajo tribal members also work on the farms, officials say.

The battle over the farms has resulted in protests and last week’s showdown in the District Court of the Navajo Nation Judicial District of Shiprock.

“We strongly urge everyone to respect the ruling of the court and move forward peacefully to ensure the safety of community members, police officers and everyone in the impacted area,” Nez said after the hearing.

Benally said in a statement that he was disappointed by the court’s decision, saying it will have a “chilling effect” on Navajo business and economic development.

But residents like Beatrice Redfeather, 75, said the hemp farms have made her fear opening her front door.

“I see marijuana plants. I see a bunch of foreign workers, armed security guards. I see a security patrol 32 feet from my front door,” Redfeather said during a court hearing last week. “Those security guards have made it known they will attack, and they have shown their guns to our family. We are mentally afraid to walk outside … The smell of marijuana is so strong that I have had to go to the hospital because of my severe headaches.”

In an investigation published Wednesday by Searchlight New Mexico, people who said they had worked on the farms described growing marijuana, and said some people who worked there were teenagers or younger. 

Legal marijuana: Pros and cons

An attorney for Benally says his client is growing hemp, a less potent form of cannabis. Products made from it are commonly used and sold across the United States at major supermarkets and convenience stores. 

Benally argued in court filings that the 2018 Farm Bill, signed into law by President Donald Trump, allows him to grow hemp on reservation land. 

But tribal leaders say harvesting both hemp and marijuana is illegal on the Navajo Nation — except for a government-backed pilot project.  Navajo law, however, has no penalty for growing hemp, Nez said, so the nation took Benally to court. 

Navajo Nation Attorney General Doreen McPaul filed a lawsuit against Benally in June, charging Benally and his company of illegally growing industrial hemp and unlawfully issuing land use permits.

Nez said tribal leaders believe the potency of Benally’s crops is well above the federal threshold that defines hemp as no more than 0.3% tetrahydrocannabinol. or THC, the main active ingredient of cannabis. 

Regardless, the controversy has prompted heated skirmishes in recent months.

Benally has hired guards who patrol the farms wearing bulletproof vests and body cameras, according to court testimony that claimed arsonists torched at least one farm. Benally’s top security officer, Duane Billey, said in court that protesters have attacked him, but his force doesn’t carry guns. Locals say otherwise.

Officials also are critical of the use of what they believe are Asian migrants who have come to the reservation during a global pandemic and camped on the farms, where they work in greenhouses. 

Sonya Sengthong, a Glendale resident whose family lives near Shiprock, said relatives have told her vans and sport utility vehicles with California and Texas license plates continually drop off what she believes are workers for the farms.

The volcanic spire, seen from town in New Mexico.

MEGAN FINNERTY/THE REPUBLIC

“We are concerned some of these visitors may be mistreating our people,” Nez said in an interview with The Arizona Republic. “There are large areas that they are using to put up housing on these farms.” 

Nez said the laborers also are breaking the law as visitors have been banned from the reservation during the COVID-19 pandemic, which has ravaged the Navajo Nation. 

Nez said he does not know when scores of workers started arriving on the reservation, adding that some live in nearby Farmington. 

“Workers are coming in and they are not citizens. They are from other areas,” Navajo Nation police Chief Philip Francisco said during last week’s hearing. “There’s a general worry about a criminal element coming in, and there’s a belief that the hemp is not hemp but marijuana.”

“We have seen a lot of Asian people working on the farms, and there’s a law in place to not allow visitors on the Navajo Nation,” Nez said in an interview. “Because of the high population of these visitors, there are concerns about human waste.”

Nez and other Navajo officials confronted some of the workers during an unannounced visit to one of the farms on Sept. 3.   “They claim they don’t speak English, so we started talking back to them in Navajo,” Nez said. 

Benally and his attorney, David Jordan, have declined to answer questions about how employees came to work on the farms. But Jordan claims the Asian workers have been racially profiled and attacked by Navajos who oppose Benally’s business venture. 

“They want to blame my client for the violent protests and that they threaten the safety of the Navajo Nation,” Jordan said in court. “But they have a fear of other people who are different.”

‘Blatant disregard’

Benally has used his position on the San Juan River Farm Board, which represents a half-dozen or so communities or chapters on the Navajo Nation, to grant land use permits to grow hemp, and his ownership of the Native American Agricultural Company to produce the crops.

The farm board on which Benally sits is composed of elected members from various chapters or communities within the Navajo Nation. Its purpose is to develop and sustain farmland and water systems for economic development.

The initial lawsuit filed against Benally says farm boards are not authorized to issue agricultural land use permits for hemp. Instead, according to Navajo law, it only is authorized to review and recommend approval of permits to the Resources Committee of the Navajo Nation Council, the legislative branch of the reservation’s government.

Tracy Raymond, a former farm board member, stated in a court filing that Benally has used his farm board position to “serve his personal interests without approval or authorization.”  “It is a great disappointment to me to have to watch those growing hemp openly flouting the law just to make a quick profit,” Raymond, a corn farmer, said.  

He added the farm board never took a vote to authorize the issuance of hemp licenses.

Benally, on his personal website, said he’s used his leadership position to “collaborate with government delegates, grazing officials, and chapter officials to protect native water rights and improve the economy and livelihood of the Navajo People.”

Benally’s business partners

His company partnered with One World Ventures, a Las Vegas-based penny-stock company with shares worth about 2 cents each, to operate the farms, financial records show. 

Some financing came from SPI Energy Co., a Hong Kong-based firm that specializes in solar panels but has diversified its portfolio.   One World Ventures placed Benally on its board in March 2019.

One World Ventures CEO DaMu Lin last year issued a news release lauding One World’s relationship with Benally’s company and the San Juan River Farm Board, stating the company was well positioned for the upcoming hemp growing season.  Calls to the company and Lin were not returned.

One World Ventures has posted combined losses of $1.48 million the past two years, financial records show.  After Benally and Lin struck a deal, they obtained financing from SPI Energy Co., a publicly traded company on the NASDAQ.

SPI launched a hemp business last year and agreed to invest $1.1 million into the Shiprock farms.   But investments from SPI dried up last year after Benally’s company failed “to deliver any of the hemp plants” and refused to return an initial instalment of $324,125, SPI financial records show. 

SPI officials visited the Shiprock farms after making their first payment by the July 31, 2019, deadline and found “the plants and growing operations appeared to be deficient and not up to industry standards,” according to a company filing. Further, SPI alleges Benally didn’t deliver updates or financial reports as required.

“Finally, NAAC failed to deliver any of the hemp plants by Nov. 30, 2019 … and refused to return the company’s down payment and to make whole the damages the company has suffered,” a filing says.

SPI said Benally’s company also did not respond to two demand letters late last year.

‘Crisis situation’

Benally — whose Facebook page describes him as a “politician” despite his losing races for Navajo Nation president and Congress — claims he’s become a political target.

Benally declined to be interviewed. Benally was scheduled to be a witness during last week’s hearing but didn’t testify. His attorney had a farm owner and a security guard to testify.

Redfeather was among those who testified against Benally. Others included Navajo Nation Environmental Protection Agency Director Oliver Whaley and the tribal police chief.   Whaley said in court that during a Sept. 9 visit to one of Benally’s farms, he found septic tanks discharging sewer water into soil and groundwater, pesticides not being properly applied and petroleum leakage. He also said Benally didn’t have permits to operate.

Francisco, the police chief, testified after Whaley and said about a year ago a “crisis situation” began in the community, noting his office has been flooded with calls to maintain peace on the Shiprock farms. All of the calls have taken officers from other emergencies, he said. 

Francisco has previously said his agency was working with the Navajo Department of Criminal Investigation and the Bureau of Indian Affairs Division of Drug Enforcement regarding potential criminal violations on the farms.

“It’s a disruption to the community, and the smell is causing problems. And there’s encroachment on people’s land,” Francisco said in court. “There has been discord and unrest.”  Residents near the farms said in court that Benally’s crews have flooded their fields, making it impossible to harvest, and destroyed a corn crop with constant dust from Benally’s operation.   Loretta Bennett, a 69-year-old farmer, said in court that the workers on Benally’s farms also don’t wear masks, and she’s concerned about the spread of COVID-19. 

Arlando Teller, an Arizona state representative from Chinle, said in an interview that while the hemp farms are in New Mexico, he’s concerned about “how the operation has taken place as far as the transparency of a business operation.”

Hemp farms may remain

Benally, a 43-year-old father of four, has said in press releases and on his website that he brought hemp farms to Shiprock as an economic driver, and he’s been successful in partnering with tribal members on his website. 

He has paid $2,000 a month to childhood friend and farmer Farley Blueyes to use up to 150 acres of his farm for hemp production.

Blueyes said his land was fallow until Benally put people to work. Security officers were needed because residents have become confrontational. 

Hoop houses at a hemp farm are visible from U.S. Highway 64 in Hogback, New Mexico, on Sept. 16, 2020.

NOEL LYN SMITH/THE FARMINGTON DAILY TIMES

Despite Friday’s ruling, the battle is likely not over. Attorneys for Benally say they will pursue “all legal channels” to keep fighting, and many Asian workers remained on the farms after Friday’s ruling.

Sengthong, the Glendale resident, said she went to visit her relatives near Shiprock on Saturday after learning about the court order.

She told The Republic that a hemp farm on a relative’s property, about 10 miles west of Shiprock, was still operating this past weekend. She said when Navajo Nation police visited the site, workers fled the farm.  Sengthong was taking pictures of the activity and said after police left, one of the workers tried to “smack” her cellphone and other workers were confrontational.   “I’ve been intimidated for what I did,” she said. “They are still working and the camp is huge.”

Benally’s attorneys said the court decision violated their client’s civil rights and put many tribal members out of work.  Jordan, Benally’s attorney, declined to say how his client would respond to the court order. Jordan said in court filings that such an order would destroy the “entire crop

Source:  https://eu.azcentral.com/story/news/local/arizona/2020/09/22 September 24, 2020

A NEW cannabis compound has been discovered and it may be 30 times more potent than THC.

Scientists aren’t yet sure whether the compound causes a high or has medical benefits so they’ve been conducting tests to try and figure this out.

Little is known about the potential effects of the new strong compound Credit: Getty – Contributor

The compound is one of two newfound cannabinoids that have been discovered in the Cannabis plant glands of the sativa L species.

Cannabinoids is the collective term for the group of diverse chemical compounds that act on the cannabinoid receptors of the brain.

THC is just one of these cannabinoids and it’s currently considered to be the principal psychoactive component of cannabis.

THC, or tetrahydrocannabinol, plugs into brain receptors and can alter our ability to co-ordinate movements, reason, record memories and perceive things like time and pleasure.

THC in cannabis is what can give smokers a high feeling Credit: Getty – Contributor

It’s thought that cannabis contains over 140 similar chemicals that can interact with receptors all over the body.

However, THC is currently the only one we know can result in a high spaced out feeling.

Of the two new cannabinoids discovered, one looks similar to the compound CBD, which isn’t psychoactive.

The other appears similar to THC but may even produce stronger mind-bending effects.

This THC lookalike is called tetrahydrocannabiphorol (THCP).

Recent research suggests that it interacts with the same brain receptor as THC but has slight differences in its chain of atoms.

The slight difference in shape of THCP means it can technically fit more snugly into its preferred brain receptor than THC.

A test showed that the compound can actually bind 30 times more reliably than THC.

When given to lab mice, the THCP made them behave as if they were on THC with slower movements and decreased reactions to pain.

The mice reached this state with a much lower dose than would have been required with THC meaning the new compound is stronger.

However, this lab experiment still doesn’t mean that the same effect would happen in humans.

THCP doesn’t appear to be present in large amounts in cannabis plants but even if it was, increased psychoactive properties would still not be guaranteed.

Being caught with cannabis comes with a maximum of five years in prison, an unlimited fine, or both.

• While being convicted of producing and supplying the Class B drug carries up to 14 years behind bars, an unlimited fine, or both.
• Police can issue a warning or on-the-spot fine if you’re caught with a small amount – generally less than one ounce – if it is deemed for personal use.

Source:  The Sun  14^th Jan. 2020

Source: Preventing Marijuana Use Among Youth & Young Adults (getsmartaboutdrugs.gov) March 2017

Cannabis Use in Pregnancy –  A Tale of 2 Concerns

In an article in JAMA, Corsi and colleagues present the results of a retrospective cohort study of 661 617 women designed to assess associations between maternal cannabis use during pregnancy and adverse obstetrical and birth outcomes.

In a matched analysis designed to control for confounding, the investigators compared 5639 self-reported cannabis users with 92 873 nonusers and found elevated rates of preterm birth (defined as gestational age <37weeks) among those who reported cannabis use. Specifically, the rates of pre term birth in the matched cohort were 10.2% vs 7.2% (risk difference, 2.98% [95% CI, 63%-3.34%]; relative risk, 1.41 [95%CI, 1.36-1.47]). While similar risks were observed for small-for-gestational-age birth and placental abruption, there appeared to be a small protective association between cannabis use and preeclampsia and gestational diabetes.

In another article in JAMA, Volkow and colleagues report findings on cannabis use among 4400 pregnant women and 133,900 nonpregnant women aged 12 to 44 years who participated in the National Survey on Drug Use and Health from 2002 to 2017. The authors documented an increase in the adjusted prevalence of cannabis use during pregnancy from 3.4%in 2002 to 7.0%in 2017—almost of all which appeared to be explained by nonmedical use.

These studies send a straightforward message: cannabis use in pregnancy is likely unsafe; with an increasing prevalence of use (presumably related to growing social acceptability and legalization in many states), its potential for harm may represent a public health problem.

This message is based on the sound, if imperfect, epidemiology of these  studies and is heightened by a misperception that marijuana is safe, as evidenced by its direct marketing to pregnant women for morning sickness despite accumulating evidence of harm.

However, there is an additional series of equally legitimate concerns, rooted more in history than epidemiology. These historical concerns relate to past and ongoing discourses on alcohol use in pregnancy and to the cocaine “epidemic that wasn’t” of the 1980s.

Both of these histories, although imperfect comparators with the emerging data on cannabis, illustrate points that provide important context to the present studies published in JAMA

First, there are issues involving the epidemiology. Randomized designs are impractical for studying risks and harms, and observational studies are prone to unmeasured confounding.

In this respect, the study by Corsi and colleagues is no different

From any other cohort study; it is, however, further limited by use of registry data, derived primarily from clinical encounters, to assess cannabis exposure.  Although the investigators performed some internal validity checks on their measurement of exposure, clinical data in the field of substance use tend to lack validation (and thus are prone to mis- classification error), particularly when unaccompanied by biological markers .  Compounding this limitation is the inability to glean from the data the timing of cannabis exposure or a dose-response relationship between exposure and out comes, both of which represent fundamental epidemiologic principles to support causality.

There was also no assessment of birth weight, which tends to be measured more accurately than gestational age.  Despite these limitations, the study is consistent with previous studies that have assessed the association between cannabis use in pregnancy and birth outcomes and provides important, population-based data.

Second, the historical context requires consideration. What has been learned from the debates about alcohol and cocaine use in pregnancy? Although it is accepted that heavy alcohol drinking during pregnancy poses an unacceptable risk to the developing foetus, the effect of moderate alcohol consumption continues to be controversial. 

On one side of this argument, those who interpret the data using a strict, by-the-numbers approach conclude that there is only minimal evidence that moderate alcohol consumption poses a demonstrable risk.

On the other side of the argument are those who interpret the data more broadly to conclude that without an empirically proven safe level of exposure, abstinence is the only reasonable advice the medical community can give to pregnant women.

One lesson of the current alcohol debate—which is often couched in terms of women’s ability to enjoy wine with dinner and thus assumes the perception of an issue that predominantly affects the privileged—is that two reasonable perspectives can be applied to the same body of opposing, non literature and reach stigmatizing conclusions.

In other words, the issue is not the data but the values that individuals bring to the data and to whom the data are thought to be most relevant.

Extrapolating this logic to the data Corsi et al present on cannabis, some might choose to focus on the reported 41% increased relative risk of pre -term birth as unacceptably high; others might choose to focus on the 2.98% absolute risk difference to be such that cannabis-related relaxation or improvement in morning sickness may not be worth abstaining from this drug.

The study by Corsi and colleagues could also be interpreted through a slightly different lens. Perhaps it represents part of an emerging story of an in utero substance exposure that is neither highly prevalent nor extremely rare, an outcome that is consequential more on a population than individual level, and an association between exposure and outcome that is moderate in both its magnitude and degree of certainty.

Unlike the “wine with dinner” debate, the dialogue on cannabis use is likely to be relevant to many sectors of society and may end up focusing on young people, especially those of colour, among whom use is markedly increasing. In these respects, a comparison with certain aspects of the history of cocaine use in pregnancy may be instructive. In 1985, the first “scientific” observation of the relationship between in utero cocaine exposure and neonatal outcomes was published. Even by the standards of its day, this study (and many that followed) were fundamentally flawed.  Yet they provided “evidence” for those in the medical community and lay press to publicly exaggerate risks of cocaine in pregnancy and to attribute (both implicitly and explicitly) lifelong disability to a large cohort of primarily minority children, for whom subsequent research demonstrated similar outcomes to unexposed children raised in similar environments.

Perhaps worse, this exaggerated risk amplified judgment and stereotype, leading to the enduring racist social constructs of the “cocaine mother” and “crackbaby” and to criminalization of substance use among pregnant women. Regrettably, the exaggerated dialogue on cocaine did little to shed light on the sequelae of urban poverty and legacy of racism in the United States. It is possible to argue that the comparisons of cannabis vs alcohol and cocaine are not entirely fair. Cocaine in particular is biologically more destructive than cannabis, universally illegal in the United States, and without health benefit.

Furthermore, the dialogue on cocaine was defined by exaggeration; so far, the dialogue on cannabis has largely been defined by a false perception of safety. While these are fair criticisms, some historic lessons of both alcohol and cocaine apply: it is impossible to separate data from the values that individuals bring to those data, no group is immune to the judgment of others, and women and minority groups (particularly pregnant women of colour) tend to bear the greatest burden of many of these judgments.

While an obvious reaction to these new data on in utero cannabis exposure is that more research is necessary, more epidemiology is unlikely to completely resolve the complex issue of potentially safe moderate use or to completely remove the tendency to imbue data interpretation with implicit biases about groups of people.

Perhaps the best reflection that can be offered is a reprise of that offered by Mayes et al in 1992. This commentary acknowledged the potential harms of prenatal cocaine exposure, dispassionately delineated the methodologic problems with the state of the literature at the time, and expressed concern that premature conclusions attributing irremediable damage in children to exposure to a single substance (isolated from the broader social milieu) were, in and of themselves, harmful. This harm, the commentary argued, accrued by way of permanently lowered expectations and by a discourse that focused on judgment and attribution as opposed to prevention and positive intervention.

The current data reported by Corsi et al and Volkow et al should spark genuine concern about the association of cannabis use in pregnancy with pre term birth. However, there should be additional concern about whether such findings may ripple through society and re-create some of the mistakes of the past.

Source:  Cannabis Use in Pregnancy: A Tale of 2 Concerns – PubMed (nih.gov) June 2019

Limited information exists on marijuana use and male reproductive health. A recent study from Duke University evaluated differences in sperm quality resulting from tetrahydrocannabinol (THC) exposure in both rats and humans. Findings suggest that paternal marijuana use, prior to conception, may present epigenetic risks to potential offspring.

…

Public perceptions pertaining to marijuana have evolved radically over the past 2 decades. While marijuana remains criminalized at the federal level, 33 states and the District of Columbia have legalized marijuana, in some capacity, for either medical or recreational use. According to the most recent National Survey on Drug Use and Health, nearly 26 million Americans, over the age of 12, currently use marijuana. While the gender gap is narrowing, men remain significantly more likely to use marijuana than women (11.7% vs. 7.3%, respectively).

In 2017, approximately 1.9 million men, between the ages of 26 and 29, reported using marijuana in the past month. Given that the average age of first-time fathers in the U.S. is around 30, these findings suggest that a substantial number of “fathers-to-be” are using marijuana at the time of conception. Little is known, however, about the impact of paternal marijuana use on reproductive outcomes.

Epigenetics, which literally translates to “above” or “on top of” genetics, refers to the biological mechanism through which genes are activated and expressed. This process acts like a light switch, turning on or off how cells read certain heritable traits written within an individual’s unique genetic code. Sperm matures continually throughout adulthood, making it particularly vulnerable to potential epigenetic modifications, such as DNA methylation, that may result from marijuana use. This study explores differences in sperm profiles, based on cannabis exposure in both humans and rats, to better understand potential heritable effects.

Key Findings

• Individuals who used marijuana can have higher and also can have significantly lower sperm concentrations, compared to those who did not, posing potential complications for fertility.

• THC-exposed sperm was associated with significantly altered DNA, in both rat and human samples.

*Associations were even stronger among individuals with higher levels of THC in their urine, implying a “dose-response relationship” such that chronic marijuana users may be impacted more severely.

• Authors identified three unique potential genetic pathways modified by THC exposure.

Looking to the Future

Past research suggests that offspring born to rats exposed to THC during adolescence demonstrate significant DNA alterations in their brains, display heightened drug-seeking behavior, and are at increased risk of developing opioid dependency over time, compared to controls. The present study is the first to extend this line of research to men of childbearing age, lending additional evidence for potential intergenerational, heritable consequences, resulting from paternal marijuana use. Just as other environmental triggers, such as air pollution, cigarette smoking, certain pesticides (i.e. DDT), and exposure to radiation are known to affect sperm health, THC may also increase the potential for genetic mutations.

For Clinicians

• Primary care physicians and healthcare professionals, both inside and outside of substance use disorder treatment landscapes, should take time to educate patients about the impact of THC on sperm so individuals may consider potential implications for fertility and children conceived during periods of active use.

For Researchers

• This article adds to a growing literature on the potential epigenetic impact of paternal marijuana use prior to conception. Findings must first be replicated in larger samples. Additionally, future longitudinal studies are necessary to explore the extent to which THC induced DNA alterations in sperm are passed down to offspring, as well as their long-term consequences.

For Policymakers

• Marijuana potency continues to increase rapidly, with THC level increasing 300% over the past 20 years. Within the current political landscape and shift towards increased access to medical and recreational marijuana, policymakers should work closely with scientists to stay informed on the extent to which increased THC levels and evolving public attitudes impact men’s reproductive health.

For General Public

• The full impact of passing THC-related DNA modifications onto offspring, and whether or not these changes are reversible is still unknown. Evidence of DNA alterations to existing Hippo signaling and Cancer genetic pathways may disrupt growth, enhance the potential for miscarriage, or impede healthy embryo development.

Methods

The authors employed a quantitative genome-scale approach, referred to as reduced representation bisulfite sequencing, to compare DNA methylation alterations in sperm across human and rat samples. A number of factors including, time since last ejaculation, semen volume, pH, morphology, and motility were controlled for across participants. Pyrosequencing, a DNA synthesizing method that relies on light detection, was implemented to identify genes with significant methylation differences. Data were then analyzed to uncover specific genetic pathways potentially impacted by paternal, preconception cannabis use.

Study Limitations

• A relatively small sample size of human subjects, limiting the generalizability of study findings.

*24 males, age 18-40 years: (12 marijuana users & 12 non-users)

• The methodological approach may fail to identify epigenetic modifications that affect multiple genes simultaneously.

Source: What you should know about Marijuana and Sperm (addictionpolicy.org) March 2019, updated October 2022

Alexandria, VA) – A new study released yesterday in the Annals of Internal Medicine found that the rise in marijuana use in Colorado since the state legalized the drug has led to increased emergency room visits. The study found that 9,973 marijuana-related emergency room visits occurred from 2012-2016, more than triple the number that occurred prior to legalization. Additionally, the study found that 10.7% of visits at UCHealth were due to the ingestion of high potency marijuana edibles. 

“Evidence continues to build the case that marijuana legalization results in harmful impacts on public health and safety,” said Dr. Kevin Sabet, founder of Smart Approaches to Marijuana and a former senior drug policy advisor to the Obama Administration. “Marijuana is no longer the weed of Woodstock. The industry is churning out new, highly potent candies, gummies, sodas, and ice creams as well as concentrates and vape pens that contain up to 99% THC. These kid-friendly products are regularly getting into the hands of children, whose developing brains are incredibly susceptible to permanent damage from this highly potent pot.”

The study found that 17% of emergency room visits were due to uncontrolled vomiting that was associated with the smoked form of the drug. Previous research has labeled this phenomenon as “scromiting,” or Cannabinoid Hyperemesis Syndrome. 12% of the visits were for acute psychosis and this was associated with high potency edibles. 8% of visits were associated with cardiovascular issues such as irregular heartbeat or even heart attacks after ingestion of edibles.

Another recent study found that the use of high potency edibles was directly linked with increases in severe mental illness, such as psychosis, and stated that if higher potency concentrates and edibles were removed from the market, instances of psychosis would be reduced by a third. 

“Lawmakers rushing to legalize marijuana need to slow down and consider the implications it could bring upon their state,” continued Dr. Sabet. “They are certainly not receiving information such as this from the pot industry’s army of lobbyists. This is why organizations such as SAM are so important. We work tirelessly to combat the industry narrative that marijuana is harmless.

Email from SAM https://www.learnaboutsam.org March 2019

Summary

Source: The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study – The Lancet Psychiatry March 2019

Abstract

Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls. We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users. Analysis of longitudinal data confirmed that GMV differences were unlikely to precede cannabis use. GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users. The distribution of GMV effects mapped onto biomarkers of the endogenous cannabinoid system providing insight into possible mechanisms for these effects.

SIGNIFICANCE STATEMENT Almost 35% of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects. We understand very little about the earliest effects of cannabis use, however, because most research is conducted in adults with a heavy pattern of lifetime use. This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence. Converging evidence suggests a role for the endocannabinoid system in these effects. This research is particularly timely as the legal status of cannabis is changing in many jurisdictions and the perceived risk by youth associated with smoking cannabis has declined in recent years.

Discussion

We present evidence of GMV differences in adolescents associated with only one or two instances of cannabis use. Although novel, this work is consistent with reports of a dose–response effect of cannabis on behavioral and brain measures following heavier use (Lorenzetti et al., 2010; Silins et al., 2014). We identified significantly greater GMV in adolescents who reported only one or two instances of cannabis use relative to cannabis naive controls in large medial temporal clusters incorporating the amygdala, hippocampus, and striatum, extending into the left prefrontal cortex. Significantly greater GMV was also observed in the lingual gyri, posterior cingulate, and cerebellum. The regions identified in this whole-brain, VBM approach replicated previous findings of differences in volume (Yücel et al., 2008; Ashtari et al., 2011; Schacht et al., 2012) and shape (Gilman et al., 2014; Smith et al., 2014, 2015) associated with cannabis use in ROI studies and with the spatial distribution of the eCB system (Burns et al., 2007). Although cannabis use has been associated with reduced brain volumes, studies typically report on adults with heavy substance use histories (cf. Ashtari et al., 2011). Gilman et al. (2014), however, have reported gray-matter density increases in the amygdala and nucleus accumbens of young adult recreational users and Medina et al. (2007) observed hippocampal enlargement in cannabis using adolescents. Our results are also consistent with the Avon Longitudinal Study of Parents and Children (French et al., 2015), which showed a trend for greater cortical thickness in male adolescents with <5 instances of cannabis use relative to THC-naive controls.

Converging evidence suggests that these effects may be a consequence of cannabis exposure. GMV differences could not be explained by group differences in demographic, personality, psychopathology, or other substance use factors. Examination of THC-naive 14-year-olds who later used cannabis showed no GMV differences, even using a more liberal ROI test, suggesting that the differences do not precede cannabis use and are not because of unidentified factors in those predisposed to use. Finally, the spatial distribution of GMV effects was associated with the eCB system, suggesting cannabis exposure may cause these findings.

The preclinical literature presents a number of possible mechanisms by which low levels of cannabis exposure could result in greater GMV relative to THC-naive controls. Adolescent rats treated with cannabinoid agonist showed altered gliogenesis in regions including the striatum and greater preservation of oligodendroglia relative to control animals (Bortolato et al., 2014). Zebra finches treated with cannabinoid agonist showed greater dendritic spine densities (Gilbert and Soderstrom, 2011); critically, these effects were observed in late-prenatal but not adult animals. Of particular relevance to this study, a single dose of Δ9THC transiently abolished eCB-mediated long-term depression (LTD) in the nucleus accumbens and hippocampus of adolescent mice (Mato et al., 2004). Suspension of LTD may interrupt maturation-related neural pruning and preserve gray matter. Future studies should assess whether these processes operate in human adolescents and whether they produce persisting alterations in GMV.

These findings should be interpreted in light of the study’s limitations. The IMAGEN sample is racially and ethnically homogenous so it remains to be determined whether the findings generalize to youth from more diverse backgrounds. Substance use was assessed using self-report and we do not have standard dose units of cannabis nor information on mode of use or a measure of drug metabolites. Combining images from different sites and imaging platforms remains controversial and is not completely controlled by including site as a covariate. Future studies should replicate the present results using images acquired at the same site on the same scanner or with equal numbers of cases and controls per scanner. We also note that the CNR1 gene expression (Hawrylycz et al., 2012) and CB₁ receptor density (D’Souza et al., 2016) maps were generated in independent samples of adults and may not accurately represent the eCB system in our sample of adolescents. Although we report significant spatial associations between GMV effects and both CNR1 gene expression and CB₁ receptor density, the effect sizes were small and any suggestion that these associations represent mechanisms for the effects we observe is speculative and requires further investigation.

We adopted a whole-brain, VBM approach to detect effects that were not limited by anatomical boundaries and to allow exploration of spatial relationships between GMV effects and the eCB system. There is evidence, however, that brain perfusion can influence VBM measures of local volume (Franklin et al., 2013, 2015; Ge et al., 2017; cf. Hawkins et al., 2018) so future studies should combine VBM with other measures of brain structure to provide confirmatory evidence. In particular, shape analysis has been shown to be sensitive to brain structural differences associated with cannabis use (Gilman et al., 2014; Smith et al., 2014, 2015; Weiland et al., 2015). Moreover, combining morphometry metrics allows for testing of associations between them, which can identify different relationships between shape deformations and local volume (Gilman et al., 2014) providing evidence of further differences between cannabis users and controls.

One source of variability in the human findings on brain structural correlates of cannabis use may be comorbid substance use (Weiland et al., 2015; Gillespie et al., 2018). Given recent evidence of different patterns of functional connectivity in groups using alcohol, nicotine, and cannabis alone and in combination (Vergara et al., 2018), it will be important to account for any possible interaction effects of cannabis with other psychoactive substances. This issue is particularly important considering the ways in which comorbid substance use has been addressed in two recent, widely cited studies. Gilman et al. (2014) covaried for alcohol and nicotine use and found gray-matter density increases and shape deformations associated with cannabis use. Weiland et al. (2015) matched groups on alcohol and nicotine use and reported no morphometric differences associated with cannabis use, concluding that previously reported differences associated with cannabis may instead be attributable to alcohol use. The participants in Weiland et al.’s (2015) study, however, were using alcohol and nicotine at higher levels than those in Gilman et al.’s (2014) study. It is possible that cannabis, alcohol, and nicotine have differential effects on brain morphometry; specifically, recreational cannabis use has been associated with volume increases, whereas alcohol has been associated with volume reductions. In the current study, we matched the groups on alcohol and nicotine use and, within the cannabis using group, neither alcohol nor nicotine use was associated with individual differences in GMV, suggesting that the GMV differences we report are associated with cannabis use.

We note individual differences in GMV effects: although regional GMV was greater at the group level for adolescents with low levels of cannabis exposure, the distributions showed a high degree of overlap such that many cannabis users had GMV equivalent to that of controls. None of the tested demographic, personality, or substance use factors stratified GMV in the cannabis users. We note evidence that an association between cannabis use and cortical thickness was stratified by genetic risk for schizophrenia (French et al., 2015) and that an association between cannabis use and hippocampal shape was stratified by dopamine-relevant genes (Batalla et al., 2018). Some adolescents may be vulnerable to GMV effects at extremely low levels of cannabis use and it will be critical to identify those at risk as these structural brain changes may be associated with individual risk for psychopathology and deleterious effects on mood and cognition.

Of the behavioral variables tested, only sensation seeking and agoraphobia differed between the cannabis users and controls and these factors were not related to GMV differences. In the cannabis using participants, GMV in the medial temporal clusters was associated with PRIQ and psychomotor speed such that greater GMV in these regions was associated with reduced performance. The finding that right medial temporal GMV predicted generalized anxiety symptoms at follow-up for those participants who had used cannabis should be interpreted with caution given the small sample size and that we were not able to identify factors that drove the individual differences in cannabis effects on GMV at baseline. These findings are notable, however, as panic and anxiety symptoms are frequently reported side effects by naive and occasional cannabis users (Hall and Solowij, 1998). We also note fMRI evidence of hypersensitivity of the amygdala to signals of threat in a partly overlapping sample of cannabis using adolescents (Spechler et al., 2015) and a relationship between adolescent cannabis use and future mood complaints (Wittchen et al., 2007), even with comparatively low levels of use (Cheung et al., 2010).

We have revealed greater GMV in adolescents with only one or two instances of cannabis use in regions rich in CB₁ receptors and CNR1 gene expression. Critically, we were able to control for a range of demographic and substance use effects, to confirm that these structural brain effects were not associated with comorbid psychopathology, and to demonstrate that these effects were unlikely to precede cannabis use. The pattern of results is characterized by individual differences in GMV effects in the cannabis users; these individual differences were associated with PRIQ and with vulnerability to future symptoms of generalized anxiety. Given the increasing levels of cannabis use among adolescents today, we suggest that studying the effects of recreational use early in life is an area of particular importance that should be addressed in the future by large scale, prospective studies.

Source: Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence | Journal of Neuroscience (jneurosci.org) March 2019

Abstract

Source: Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends – Albert Stuart Reece, Gary Kenneth Hulse, 2019 (sagepub.com) July 2019

A growing number of countries are deciding to ditch prohibition. What comes next?

In an anonymous-looking building a few minutes’ drive from Denver International Airport, a bald chemotherapy patient and a pair of giggling tourists eye the stock on display. Reeking packets of mossy green buds—Girl Scout Cookies, KoolAid Kush, Power Cheese—sit alongside cabinets of chocolates and chilled drinks. In a warehouse behind the shop pointy-leaved plants bask in the artificial light of two-storey growing rooms. Sally Vander Veer, the president of Medicine Man, which runs this dispensary, reckons the inventory is worth about $4m.

America, and the world, are going to see a lot more such establishments. Since California’s voters legalised the sale of marijuana for medical use in 1996, 22 more states, plus the District of Columbia, have followed suit; in a year’s time the number is likely to be nearer 30. Sales to cannabis “patients” whose conditions range from the serious to the notional are also legal elsewhere in the Americas (Colombia is among the latest to license the drug) and in much of Europe. On February 10th Australia announced similar plans.

Now a growing number of jurisdictions are legalising the sale of cannabis for pure pleasure—or impure, if you prefer. In 2014 the American states of Colorado and Washington began sales of recreational weed; Oregon followed suit last October and Alaska will soon join them. They are all places where the drug is already popular (see chart 1). Jamaica has legalised ganja for broadly defined religious purposes. Spain allows users to grow and buy weed through small collectives. Uruguay expects to begin non-medicinal sales through pharmacies by August.  

Canada’s government plans to legalise cannabis next year, making it the first G7 country to do so. But it may not be the largest pot economy for long; California is one of several states where ballot initiatives to legalise cannabis could well pass in America’s November elections. A majority of Americans are in favour of such changes (see chart 2).

Legalisers argue that regulated markets protect consumers, save the police money, raise revenues and put criminals out of business as well as extending freedom. Though it will be years before some of these claims can be tested, the initial results are encouraging: a big bite has been taken out of the mafia’s market, thousands of young people have been spared criminal records and hundreds of millions of dollars have been legitimately earned and taxed. There has so far been no explosion in consumption, nor of drug-related crime.

To get the most of these benefits, though, requires more than just legalisation. To live outside the law, Bob Dylan memorably if unconvincingly claimed, you must be honest; to live inside it you must be regulated. Ms Vander Veer points to a “two-inch thick” book of rules applicable to Medicine Man’s business.

Such rules should depend on which of legalisation’s benefits a jurisdiction wants to prioritise and what harms it wants to minimise. The first consideration is how much protection users need. As far as anyone has been able to establish (and some have tried very hard indeed) it is as good as impossible to die of a marijuana overdose. But the drug has downsides. Being stoned can lead to other calamities: in the past two years Colorado has seen three deaths associated with cannabis use (one fall, one suicide and one alleged murder, in which the defendant claims the pot made him do it). There may have been more. Colorado has seen an increase in the proportion of drivers involved in accidents who test positive for the drug, though there has been no corresponding rise in traffic fatalities.

The chronic harm done by the drug is still a matter for debate. Heavy cannabis use is associated with mental illness, but researchers struggle to establish the direction of causality; a tendency to mental illness may lead to drug use. It may also be the case that some are more susceptible to harm than others.

Jonathan Caulkins of Carnegie Mellon University has found that cannabis users are more likely than alcohol drinkers to say the drug has caused them problems at work or at home. It is an imperfect comparison because most cannabis users are, by definition, lawbreakers, and therefore perhaps more prone to such problems. Nonetheless it is clear that pot is, in Mr Caulkins’ words, a “performance-degrading drug”.

What’s more, some struggle to give it up: in America 14% of people who used pot in the past month meet the criteria by which doctors define dependence. As in the alcohol and tobacco markets, about 80% of consumption is accounted for by the heaviest-using 20% of users. Startlingly, Mr Caulkins calculates that in America more than half of all cannabis is consumed by people who are high for more than half their waking hours.

To complicate matters, the public-health effects of cannabis should not be looked at in isolation. If taking up weed made people less likely to consume cigarettes or alcohol it might offer net benefits. But if people treat cannabis and other drugs as complements—that is, if doing more pot makes them smoke more tobacco or guzzle more alcohol—an increase in use could be a big public-health problem.

No one yet knows which is more likely. A review of mostly American studies by the RAND Corporation, a think-tank, found mixed evidence on the relationship between cannabis and alcohol. Demand for tobacco seems to go up along with demand for cannabis, though the two are hard to separate because, in Europe at least, they are often smoked together. The data regarding other drugs are more limited. Proponents of the Dutch “coffee shop” system, which allows purchase and consumption in specific places, argue that legalisation keeps users away from dealers who may push them on to harder substances. And there is some evidence that cannabis functions as a substitute for prescription opioids, such as OxyContin, which kill 15,000 Americans each year. People used to worry that cigarettes were a “gateway” to cannabis, and that cannabis was in turn a gateway to hard drugs. It may be the reverse: cannabis could be a useful restraint on the abuse of opioids, but a dangerous pathway to tobacco.

More bong for your buck

Danger and harm are not in themselves a reason to make or keep things illegal. But the available evidence persuades many supporters of legalisation that cannabis consumption should still be discouraged. The simplest way to do so is to keep the drug expensive; children and heavy users, both good candidates for deterrence, are particularly likely to be cost sensitive. And keeping prices up through taxes has political appeal that goes beyond public health. Backers of California’s main legalisation measure make much of the annual $1 billion that could flow to state coffers.

Setting the right level for the tax, though, is challenging. Go too low and you encourage use. Aim too high and you lose one of the other benefits of legalisation: closing down a criminal black market.

Comparing Colorado and Washington illustrates the trade-off. Colorado has set its pot taxes fairly low, at 28% (including an existing sales tax). It has also taken a relaxed approach to licensing sellers; marijuana dispensaries outnumber Starbucks. Washington initially set its taxes higher, at an effective rate of 44%, and was much more conservative with licences for growers and vendors. That meant that when its legalisation effort got under way in 2014, the average retail price was about $25 per gram, compared with Colorado’s $15. The price of black-market weed (mostly an inferior product) in both states was around $10.

The effect on crime seems to have been as one would predict. Colorado’s authorities reckon licensed sales—about 90 tonnes a year—now meet 70% of total estimated demand, with much of the rest covered by a “grey” market of legally home-grown pot illegally sold. In Washington licensed sales accounted for only about 30% of the market in 2014, according to Roger Roffman of the University of Washington. Washington’s large, untaxed and rather wild-west “medical” marijuana market accounts for a lot of the rest. Still, most agree that Colorado’s lower prices have done more to make life hard for organised crime.

Uruguay also plans to set prices comparable to those that illegal dealers offer. “We intend to compete with the illicit market in price, quality and safety,” says Milton Romani, secretary-general of the National Drug Board. To avoid this competitively priced supply encouraging more use, the country will limit the amount that can be sold to any particular person over a month. In America, where such restrictions (along with the register of consumers needed to police them) would probably be rejected, it will be harder to stop prices for legal grass low enough to shut down the black market from also encouraging greater use. Indeed, since legalisation consumption in Colorado appears to have edged up a few percentage points among both adults and under-21s, who in theory shouldn’t be able to get hold of it at all; that said, a similar trend was apparent before legalisation, and the data are sparse.

If, starved of sales, the black market shrinks beyond a point of no return, taxes could later go up, restoring the deterrent. There is precedent for this. When the prohibition of alcohol ended in 1933, Joseph Choate of America’s Federal Alcohol Control Administration recommended “keeping the tax burden on legal alcoholic beverages comparatively low in the earlier post-prohibition period in order to permit the legal industry to offer more severe competition to its illegal competitor.” After three years, he estimated, with the mob “driven from business, the tax burden could be gradually increased.” And so it was (see chart 3).

Those taxes reflected the strength of what was for sale; taxing whiskey more than beer made sense as a deterrent to drunkenness. Here, so far, the regulation of cannabis lags behind. The levies on price or weight used by America’s legalising states are easy to administer, but could push consumers towards stronger strains. In the various lines sold by Medicine Man, for example, the concentration of tetrahydrocannabinol (THC), the chemical compound that gets you high, varies from 7% to over 20%. The prices, though, are mostly the same, and there is no difference in tax. Some like it weak, but on the whole, Ms Vander Veer says, the stronger varieties are what people ask for. If they cost no more, why not? The average potency on sale in Denver is now about 18%, roughly three times the strength of the smuggled Mexican weed that once dominated the market.

Barbara Brohl, the head of Colorado’s Department of Revenue, says THC-based taxation is something the state may try in the future. But the speed with which the regulatory apparatus was set up—sales began just over a year after the ballot initiative passed in November 2012—meant that they had to move fast. “We’re building the airplane while we’re in the air,” she says. Uruguay, clear that it wants to be “a regulated market, not a free market”, as Mr Romani puts it, plans a more direct way of discouraging the stronger stuff. Dispensaries will sell just three government-approved strains of cannabis, their potencies ranging from 5% to 14%.

Another issue for regulators is the increasing number of ways in which cannabis is consumed. The star performer of the legalised pot market is the “edibles” sector, which includes THC-laced chocolates, drinks, lollipops and gummy bears. There are also concentrated “tinctures” to be dropped onto the tongue and vaping products to be consumed through e-cigarettes. Foria, a California company, sells a THC-based personal lubricant (“For all my vagina knew, I was laying on one of San Diego’s fabulous beaches!” reads one testimonial).

The popularity of these products looks set to grow; users appreciate the discretion with which they can be consumed, producers like the ease with which their production can be automated (no hand-picking of buds required). But edibles, in particular, make it easy to take more than intended. A hit on a joint kicks in quickly; cakes or drinks can take an hour or two. Inexperienced users sometimes have a square of chocolate, feel nothing and wolf down the rest of the bar—only to spend the next 12 hours believing they are under attack by spiders from Mars.

The three cannabis-related deaths in Colorado all followed the consumption of edibles. Hospitals in the state also report seeing an increasing number of children who have eaten their parents’ grown-up gummy bears. In response the authorities have tightened their rules on packaging, demanding clearer labelling, childproof containers, and more obvious demarcation of portions.

A second concern about new ways of taking the drug is that they could attract new customers. Ms Vander Veer says that edibles offer a “good way to get comfortable with how THC makes you feel”; women, older people and first-timers are particularly keen on them. If you see cannabis as a harmless high, this is not a problem. If you want to keep usage low, it is.

The innovation seen to date is just a taste of what entrepreneurs might eventually dream up. On landing in Denver—which, uncoincidentally, is now the most popular spring-break destination for American students—you can call a limo from 420AirportPickup which will drive you to a dispensary and then let you smoke in the back while you cruise on to a cannabis-friendly hotel (some style themselves “bud ‘n’ breakfast”). You can take a marijuana cookery course, or sign up for joint-rolling lessons. Dispensaries offer coupons, loyalty points, happy hours and all the other tricks in the marketing book.

Legalisation has also paved the way for better branding. Snoop Dogg, a rap artist, has launched a range of smartly packaged products called “Leafs by Snoop”. The estate of Bob Marley has lent its name to a range of “heirloom marijuana strains” supposedly smoked by the man himself.

Roll up for the mystery tour

Branding means advertising, which may itself promote use. Many in America would like to follow Uruguay’s example and ban all cannabis advertising, but the constitution stands in their way. When Colorado banned advertising in places where more than 30% of the audience is likely to be under-age cannabis companies objected on the grounds of their right to free speech, though the suit was later dropped.

As well as moving into advertising, the industry is growing more professional in its lobbying. In legalisation initiatives the “Yes” side increasingly outspends the “No” side: in Alaska by four to one, in Oregon by more than 50 to one. Rich backers help—in California Sean Parker, an internet billionaire, has donated $1m to the cause. In some states, ballot initiatives have been heavily influenced by the very people who are hoping to sell the drugs once they are legalised. In November 2015 voters in Ohio soundly rejected a measure that would have granted a cannabis-cultivation oligopoly to the handful of firms that had backed it.

Worries about regulatory capture will increase along with the size of the businesses standing to gain. Big alcohol and tobacco firms currently deny any interest in the industry. But they said the same in the 1960s and 1970s, a time when Philip Morris and British American Tobacco, it has since been revealed, were indeed looking at the market. Brendan Kennedy, the chief executive of Privateer Holdings, a private-equity firm focused on the marijuana industry, says that several alcohol distributors have invested in American cannabis firms.

Even without such intervention big companies are likely to emerge. Sam Kamin, a law professor at Denver University who helped draft Colorado’s regulations, suspects that eventual federal legalisation, which would make interstate trade legal, could well see cannabis cultivation become something like the business of growing hops, virtually all of which come from Washington, Oregon and Idaho. Big farms supplying a national market would be much cheaper than the current local-warehouse model, driving local suppliers out of the market, or at least into a niche.

The industry has so far been helped by the fact that many on the left who might normally campaign against selling harmful substances to young people are vocal supporters of legalisation. That could change with the growth of a business lobby that, although understanding that an explosion in demand would trigger a backlash, may have little long-term interest in restraint. The prospect of such a lobby could also serve as an incentive for states to take the initiative on legalisation, rather than waiting for their citizens to demand it. Fine-tuning Colorado’s regime, Mr Kamin says, has been made harder by the fact that the ballot of 2012 enshrined legalisation in the state constitution. Other states “might want [their rules] to be defined instead by legislation, not citizens’ initiative,” suggests Ms Brohl, the Colorado tax chief.

Different places will legalise in different ways; some may never legalise at all; some will make mistakes they later think better of. But those that legalise early may prove to have a lasting influence well beyond their borders, establishing norms that last for a long while. It behoves them to think through what needs regulating, and what does not, with care. Over-regulation risks losing some of the main benefits of liberalisation. But as alcohol and tobacco show, tightening regimes at a later date can be very difficult indeed.

Source:  http://www.economist.com/news/briefing/21692873   13 Feb. 2016

Abstract

Three decades ago, I would have been over the moon to see marijuana legalized. It would have saved me a lot of effort spent trying to avoid detection, constantly looking for places to hide a joint. I smoked throughout my teens and early 20s. During this period, upon landing in a new city, my first order of business was to score a quarter-ounce. The thought of a concert or a vacation without weed was simply too bleak.

These days it’s hard to find anybody critical of marijuana.

The drug enjoys broad acceptance by most Americans — 63 percent favoured ending cannabis prohibition in a recent Quinnipiac poll — and legislators on both sides of the aisle are becoming more likely to endorse than condemn it. After years of loosening restrictions on the state level, there are signs that the federal government could follow suit: In April, Senate Minority Leader Charles E. Schumer (D-N.Y.) became the first leader of either party to support decriminalizing marijuana at the federal level, and President Trump (his attorney general notwithstanding) promised a Republican senator from Colorado that he would protect states that have legalized pot.

And why not? The drug is widely thought to be either benign or beneficial. Even many of those apathetic toward its potential health benefits are ecstatic about its commercial appeal, whether for personal profit or state tax revenue. Legalization in many cases, and for many reasons, can be a good thing. I’m sympathetic.

But I am also a neuroscientist, and I can see that the story is being oversimplified. The debate around legalization — which often focuses on the history of racist drug laws and their selective enforcement — is astoundingly naive about how the widespread use of pot will affect communities and individuals, particularly teenagers. In our rush to throw open the gate, we might want to pause to consider how well the political movement matches up with the science, which is producing inconveniently alarming studies about what pot does to the adolescent brain.

Marijuana for sale at a Colorado dispensary.    (Matthew Staver/Bloomberg Creative Photos)

I took a back-door route to the science of marijuana, starting with a personal investigation of the plant’s effects. When I was growing up in South Florida in the 1980s, pot was readily available, and my appreciation quickly formed the basis for an avid habit. Weed seemed an antidote to my adolescent angst and ennui, without the sloppiness of alcohol or the jaw-grinding intensity of stimulants.

Of the many things I loved about getting high, the one I loved best was that it commuted the voice in my head — usually peevish or bored — to one full of curiosity and delight. Marijuana transformed the mundane into something dramatic: family outings, school, work or just sitting on the couch became endlessly entertaining when I was stoned.

Like any mind-altering substance, marijuana produces its effects by changing the rate of what is already going on in the brain. In this case, the active ingredient delta-9-THC substitutes for your own natural endocannabinoids and mimics their effects. It activates the same chemical processes the brain employs to modulate thoughts, emotions and experiences. These specific neurotransmitters, used in a targeted and judicious way, help us sort the relentless stream of inputs and flag the ones that should stand out from the torrent of neural activity coding stray thoughts, urges and experience. By flooding the entire brain, as opposed to select synapses, marijuana can make everything, including the most boring activities, take on a sparkling transcendence.

Why object to this enhancement? As one new father told me, imbibing made caring for his toddler much more engrossing and thus made him, he thought, a better parent. Unfortunately, there are two important caveats from a neurobiological perspective.

As watering a flooded field is moot, widespread cannabinoid activity, by highlighting everything, conveys nothing. And amid the flood induced by regular marijuana use, the brain dampens its intrinsic machinery to compensate for excessive stimulation. Chronic exposure ultimately impairs our ability to imbue value or importance to experiences that truly warrant it.

In adults, such neuro-adjustment may hamper or derail a successful and otherwise fulfilling life, though these capacities will probably recover with abstinence. But the consequences of this desensitization are more profound, perhaps even permanent, for adolescent brains. Adolescence is a critical period of development, when brain cells are primed to undergo significant organizational changes: Some neural connections are proliferating and strengthening, while others are pared away.

Although studies have not found that legalizing or decriminalizing marijuana leads to increased use among adolescents, perhaps this is because it is already so popular. More teenagers now smoke marijuana than smoke products with nicotine; between 30 and 40 percent of high school seniors report smoking pot in the past year, about 20 percent got high in the past month, and about 6 percent admit to using virtually every day. The potential consequences are unlikely to be rare or trivial.

The decade or so between puberty and brain maturation is a critical period of enhanced sensitivity to internal and external stimuli. Noticing and appreciating new ideas and experiences helps teens develop a sense of personal identity that will influence vocational, romantic and other decisions — and guide their life’s trajectory. Though a boring life is undoubtedly more tolerable when high, with repeated use of marijuana, natural stimuli, like those associated with goals or relationships, are unlikely to be as compelling.

It’s not surprising, then, that heavy-smoking teens show evidence of reduced activity in brain circuits critical for  flagging newsworthy experiences, are 60 percent less likely to graduate from high school, and are at substantially increased risk for heroin addiction and alcoholism. They show alterations in cortical structures associated with impulsivity and negative moods; they’re seven times more likely to attempt suicide.

Recent data is even more alarming: The offspring of partying adolescents, specifically those who used THC, may be at increased risk for mental illness and addiction as a result of changes to the epigenome — even if those children are years away from being conceived. The epigenome is a record of molecular imprints of potent experiences, including cannabis exposure, that lead to persistent changes in gene expression and behavior, even across generations. Though the critical studies are only now beginning, many neuroscientists prophesize a social version of Rachel Carson’s “Silent Spring,” in which we learn we’ve burdened our heirs only generations hence.

Might the relationship between marijuana exposure and changes in brain and behavior be coincidence, as tobacco companies asserted about the link between cancer and smoking, or does THC cause these effects? Unfortunately, we can’t assign people to smoking and nonsmoking groups in experiments, but efforts are underway to follow a large sample of children across the course of adolescent development to study the effects of drug exposure, along with a host of other factors, on brain structure and function, so future studies will probably be able to answer this question.

In the same way someone who habitually increases the volume in their headphones reduces their sensitivity to birdsong, I followed the “gateway” pattern from pot and alcohol to harder drugs, leaping into the undertow that eventually swept away much of what mattered in my life. I began and ended each day with the bong on my nightstand as I floundered in school, at work and in my relationships. It took years of abstinence, probably mirroring the duration and intensity of my exposure, but my motivation for adventure seems largely restored. I’ve been sober since 1986 and went on to become a teacher and scholar. The single-mindedness I once directed toward getting high came in handy as I worked on my dissertation. I suspect, though, that my pharmacologic adventures left their mark.

Now, as a scientist, I’m unimpressed with many of the widely used arguments for the legalization of marijuana. “It’s natural!” So is arsenic. “It’s beneficial!” The best-documented medicinal effects of marijuana are achieved without the chemical compound that gets users high. “It’s not addictive!”  This is false, because the brain adapts to marijuana as it does to all abused drugs, and these neural adjustments lead to tolerance, dependence and craving — the hallmarks of addiction.

It’s true that a lack of benefit, or even a risk for addiction, hasn’t stopped other drugs like alcohol or nicotine from being legal, used and abused. The long U.S. history of legislative hypocrisy and selective enforcement surrounding mind-altering substances is plain to see. The Marihuana Tax Act of 1937, the first legislation designed to regulate pot, was passed amid anti-Mexican sentiment (as well as efforts to restrict cultivation of hemp, which threatened timber production); it had nothing do with scientific evidence of harm. That’s true of most drug legislation in this country. Were it not the case, LSD would be less regulated than alcohol, since the health, economic and social costs of the latter far outweigh those of the former. (Most neuroscientists don’t believe that LSD is addictive; its potential benefits are being studied at Johns Hopkins and New York University, among other places.)

Still, I’m not against legalization. I simply object to the astounding lack of scepticism about pot in our current debate. Whether or not to legalize weed is the wrong question. The right one is: How will growing use of delta-9-THC affect individuals and communities?

Though the evidence is far from complete, wishful thinking and widespread enthusiasm are no substitutes for careful consideration. Instead of rushing to enact new laws that are as nonsensical as the ones they replace, let’s sort out the costs and benefits, using current scientific knowledge, while supporting the research needed to clarify the neural and social consequences of frequent use of THC. Perhaps then we’ll avoid practices that inure future generations to what’s really important.

                                       By Judith Grisel,    May 25, 2018

Source:  https://www.washingtonpost.com/ posteverything/wp/2015/04/30/yes-pot-should-be-legal-but-it-shouldnt-be-sold-for-a-profit/   

(Denver, CO) – Today, a new study on the impact of marijuana legalization in Colorado conducted by the Centennial Institute found that for every one dollar in tax revenue from marijuana, the state spends $4.50 as a result of the effects of the consequences of legalization.

This study used all available data from the state on hospitalizations, treatment for Cannabis Use Disorder (CUD), impaired driving, black market activity, and other parameters to determine the cost of legalization. Of course, calculating the human cost of addiction is nearly impossible, we can assume the cost estimated for treating CUD is a gross underestimate due to the fact that it is widely believed among health officials that CUD goes largely untreated…yet rates have been increasing significantly in the past decade.

That, in conjunction with the fact that there is no way of quantifying the environmental impact the proliferation of single use plastic packaging common within the marijuana industry, leads us to believe this is indeed a very conservative estimate.

“Studies such as this show that the only people making money off the commercialization of marijuana are those in the industry who profit at the expense of public health and safety,” said Dr. Kevin Sabet, president of Smart Approaches to Marijuana (SAM). “The wealthy men in suits behind Big Marijuana will laugh all the way to the bank while minority communities continue to suffer, black markets continue to thrive, and taxpayers are left to foot the bill.”

“The data collected in this study, as in similar studies before it, continues to show the scope of the cost of commercialization. The effects of legalization are far and wide, and affect just about every resident in the state directly and indirectly,” said Jeff Hunt, Vice President of Public Policy for Colorado Christian University.

“The pot industry doesn’t want this dirty truth to be seen by law makers and the taxpayers, who were promised a windfall in tax revenue,” said Justin Luke Riley, president of the Marijuana Accountability Coalition. “The MAC will continue to shine a light on the industry and urge our lawmakers to reign in Big Pot before it brings more harm on Coloradans.”

Source: New Colorado Report: Cost of Marijuana Legalization Far Outweighs Tax Revenues – Smart Approaches to Marijuana (learnaboutsam.org) November 2018

Fullerton, California, police officer Jae Song conducts a field sobriety test on a driver suspected of driving while impaired by marijuana. A growing number of drugged drivers have been killed in crashes. Bill Alkofer/The Orange County Register/SCNG via AP

As legal marijuana spreads and the opioid epidemic rages on, the number of drugged drivers killed in car crashes is rising dramatically, according to a report released today.

Forty-four percent of fatally injured drivers tested for drugs had positive results in 2016, the Governors Highway Safety Association found, up more than 50 percent compared with a decade ago. More than half the drivers tested positive for marijuana, opioids or a combination of the two.

“These are big-deal drugs. They are used a lot,” said Jim Hedlund, an Ithaca, New York-based traffic safety consultant who conducted the highway safety group’s study. “People should not be driving while they’re impaired by anything and these two drugs can impair you.”

Nine states and Washington, D.C., allow marijuana to be sold for recreational and medical use, and 21 others allow it to be sold for medical use. Opioid addiction and overdoses have become a national crisis, with an estimated 115 deaths a day.

States are struggling to get a handle on drugged driving. Traffic safety experts say that while it’s easy for police to test drivers for alcohol impairment using a breathalyzer, it’s much harder to detect and screen them for drug impairment.

There is no nationally accepted method for testing drivers, and the number of drugs to test for is large. Different drugs also have different effects on drivers. And there is no definitive data linking drugged driving to crashes.

“With alcohol, we have 30 years of research looking at the relationship between how much alcohol is in a person’s blood and the odds they will cause a traffic crash,” said Jake Nelson, AAA’s traffic safety director. “For drugs, that relationship is not known.”

Another problem is that drivers often are using more than one drug at once. The new study found that about half of drivers who died and tested positive for drugs in 2016 were found to have two or more drugs in their system.

Alcohol is also part of the mix, the report found: About half the dead drivers who tested positive for alcohol also tested positive for drugs.

Drug Testing Varies

More than 37,000 people died in vehicle crashes in 2016, up 5.6 percent from the previous year, according to the National Transportation Highway Safety Administration.

Using fatality data from the federal agency, Hedlund, the governors’ highway safety group’s consultant, found that 54 percent of fatally injured drivers that year were tested for drugs and alcohol. Of those who had drugs in their system, 38 percent tested positive for marijuana, 16 percent for opioids and 4 percent for both. The remaining 42 percent tested positive for a variety of legal and illegal drugs, such as cocaine and Xanax.

That means more than 5,300 drivers who died in fatal crashes in 2016 tested positive for drugs, Hedlund said. Those numbers don’t include all drivers killed in crashes or those who drove impaired but didn’t have a crash.

Driver drug testing varies from state to state. States don’t all test for the same drugs or use the same testing methods.

“A lot of the tools we developed for alcohol don’t work for drugs,” said Russ Martin, government relations director for the highway safety group. “We don’t have as clear a method for every officer to conduct roadside tests.”

Police who stop drivers they think are impaired typically use standard sobriety tests, such as asking the person to walk heel to toe and stand on one leg. That works well for alcohol testing, as does breathing into a breathalyzer, which measures the blood alcohol level.

But these standard sobriety tests don’t work for drugs, which can only be detected by testing blood, urine or saliva. Even then, finding the presence of a drug doesn’t necessarily mean the person is impaired.

With marijuana, for example, metabolites can stay in the body for weeks, long after impairment has ended, making it difficult to determine when the person used the drug.

States have dealt with drugged driving in different ways. In every state it is illegal to drive under the influence of drugs, but some have created zero tolerance laws for some drugs, whereas others have set certain limits for marijuana or some other drugs.

That creates another challenge because policymakers are trying to make changes that aren’t necessarily based on research, said Richard Romer, AAA’s state relations manager.

“The presence of marijuana doesn’t necessarily mean impairment,” Romer said. “You could be releasing drivers who are dangerous and imprisoning people who are not impaired.”

State Statistics

In Colorado, the first state to legalize recreational marijuana, there were 51 fatalities in 2016 that involved drivers with THC blood levels above the state’s legal limit, according to the state department of transportation. THC is the main active ingredient in marijuana, and causes the euphoria associated with the drug.

An online survey in April by the department found that 69 percent of pot users said they had driven under the influence of marijuana at least once in the past year and 27 percent said they drove high almost daily. Many recreational users said they didn’t think it affected their ability to drive safely.

In Washington state, a 2016 report by the AAA Foundation for Traffic Safety found that fatal crashes of drivers who recently used marijuana doubled after the state legalized it.

The governors’ highway safety group is recommending that states offer advanced training to a majority of patrol officers about how to recognize drugged drivers at the roadside.

Officers in some states already are using a battery of roadside tests that focus on physiological symptoms, such as involuntary eye twitches, pulse rate and muscle tone, to determine whether a driver is impaired by drugs. And at the police station, some officers trained as drug examiners do a more extensive series of tests to identify the type of drug.

The safety group also wants states to launch a campaign to educate the public about how drugs can impair driving and work with doctors and pharmacists to make patients aware of the risks of driving while using prescription medications such as opioids.

And it is calling on states and the federal government to compile better data on drugged driving, including testing all drivers killed in crashes for drugs and alcohol.

“Not every driver in a fatal crash is tested. And plenty of drivers out there haven’t crashed and haven’t been tested,” Martin said. “We have good reason to believe there are more drug-impaired drivers out there than the data shows.”

Source: Drugged Driving Deaths Spike With Spread of Legal Marijuana, Opioid Abuse – Stateline May 2018

Tell Your Children:
The Truth About Marijuana, Mental Illness, and Violence
by alex berenson
free press, 272 pages, $26

The smoking of marijuana, with its careful preparation of the elements and the solemn passing around of the shared joint, was the unholy communion of the counterculture in the late 1960s, when our present elite formed its opinions. Many of them allowed their children to follow their bad examples, and resent that this exposes their young to a (tiny) risk of persecution and career damage. As a result, those who still disapprove of marijuana are much disliked. The book I wrote on the subject six years ago, The War We Never Fought, received a chilly reception and remains so obscure that I don’t think Alex ­Berenson, whose book has received much friendlier coverage, even knows it exists. As a writer who naturally covets readers and sales, I find this mildly infuriating.

But let me say through clenched teeth that it is of course very good news that a fashionable young metropolitan person such as Mr. ­Berenson is at last prepared to say openly that marijuana is a dangerous drug whose use should be severely discouraged. For, as ­Berenson candidly admits, he was until recently one of the great complacent mass of bourgeois bohemians who are pretty relaxed about it. He confesses in the most important passage in the book that he once believed what most of such people believed. He encapsulates this near-universal fantasy thus:

Marijuana is safe. Way safer than alcohol. Barack Obama smoked it. Bill Clinton smoked it too, even if he didn’t inhale. Might as well say it causes presidencies. I’ve smoked it myself, I liked it fine. Maybe I got a little paranoid, but it didn’t last. Nobody ever died from smoking too much pot.

These words are a more or less perfect summary of the lazy, ignorant, self-serving beliefs of highly educated, rather stupid middle-class metropolitans all over the Western world in such places as, let’s just say for example, the editorial offices of the New York Times. Thirty years from now (when it’s too late), they will look as crass and irresponsible as those magazine advertisements from the 1950s in which pink-faced doctors wearing white coats recommended certain brands of cigarettes. But just now, we are in that foggy zone of consciousness where the truth is known to almost nobody except those with a certain kind of direct experience, and can be ignored by everyone else.

One of the experienced ones, thank heaven, is Alex ­Berenson’s wife Jacqueline. She is a psychiatrist who specializes in evaluating mentally ill criminals. One evening, the Berensons were discussing one of her cases, a patient who had committed a terrible, violent act. Casually, Jacqueline remarked, “Of course he was high, been smoking pot his whole life.” Alex doubtfully interjected, “Of course?,” and she replied, “Yeah, they all smoke.” (She didn’t mean tobacco.) And she is right. They all do. You don’t need to be a psychiatrist to know this. You just have to be able to do simple Internet searches.

Most violent crime is scantily reported, since local newspapers lack the resources they once had. The exceptions are rampage mass killings by terrorists (generally in Europe) and non-political crazies (more common in the United States). These crimes are intensively reported, to such an extent that news media find things out they were not even looking for, such as the fact that the perpetrator is almost always a long-term marijuana user. Where he isn’t (and it is almost always a he), some other legal or illegal psychotropic, such as steroids or “antidepressants,” is ­usually in evidence. But you do have to look, and most people don’t. Then you have to see a pattern, one that a lot of important, influential people specifically do not want to see.

That husband-and-wife conversation in the Berenson apartment is the whole book in a nutshell, the epiphany of a former apostle of complacency from the college-­educated classes who suddenly discovers what has been going on around him for years. What he repeats over and over again is very simple: Marijuana can make you permanently crazy. (This is a long-term cumulative effect, not the effect of immediate intoxication.) And once it has made you crazy, it can make you violent, too.

You’ll only find out if you’re susceptible by taking it. It is not soft. It is not safe. It is one of the most dangerous drugs there is, and we are on the verge of allowing it to be advertised and put on open sale. Berenson has gotten into predictable trouble for asserting that the connection is pretty much proved. Alas, this is not quite so. But the correlation is hugely powerful. The chance that it is meaningful is great. Who would be surprised if a drug with powerful psychotropic effects turned out to be the cause of mental illness in its users? Correlation is not causation, but it is one of the main tools of ­epidemiology. Causation, ­especially in matters of the brain, is extraordinarily difficult to prove, and so we may have to base our actions, or our refusals to take action, on something short of total certainty.

Tell Your Children is filled with persuasive, appalling individual case histories of wild violence, including the abuse of small children. It also lists and explains the significance of powerful, large-scale surveys of Swedish soldiers and New Zealand students, which connect the drug to mental illness and lowered school performance. Berenson provides facts and statistics about violent crime in places where marijuana is widely available, and anecdotes so repetitive that they cease to be anecdotes. The puzzle remains as to why it is necessary to say all this repeatedly when a sensible person would listen the first time.

Perhaps it is because of the large, and very well-funded, campaigns for marijuana legalization described by Berenson. People who drink fair-trade coffee and eat vegan, who loathe other greed lobbies—such as pharmaceuticals, tobacco, fast food, or sugary drinks—smile on this campaign to make money from the misery of others.

Berenson shows how mental illness has grown in our midst without being noticed in public statistics. A comparable growth in, say, measles or tuberculosis would have shown up. But deteriorating mental health does not, thanks to privacy concerns, and to the fact that mental illness is not easily classified. It is also a sad truth that rich, advanced Western societies nowadays begrudge money for the mental hospitals needed to house and protect those who have overthrown their own minds. They are reluctant to record the existence and prevalence of the very real suffering that ought to be treated in the hospitals they have sold off, demolished, or never built.

Berenson also witheringly describes the propaganda devised by those who want to legalize the drug, from the mind-expanding zealots who view drug use as liberating to the hard-headed entrepreneurs and political professionals. Argue against them at your peril. Your audience may learn something, but your opponents will not. Wilful ignorance is the most powerful barrier to communication. It seals the human mind up like a fortress. You might as well read the works of Jean-Paul Sartre to a hungry walrus as try to debate with such people. I have attempted it. They don’t hear a word you say, but they hate you for getting in their way.

Berenson gives a fairly thorough account of the “medical marijuana” campaign, an almost comically absurd attempt to portray a poison as a medicine. This campaign is so bogus that it will vanish from the earth within days of full legalization, because in truth there is very little evidence that marijuana-based medicines are of much use. Berenson quotes one refreshingly candid marijuana defender as admitting, “Six percent of all marijuana users use it for medical purposes. Medical marijuana is a way of protecting a subset of society from arrest.”

In the U.S., legalizers are poised to win the modern civil war over the legalization of marijuana which has been dividing the country for half a century. It looks now as if marijuana will soon be legalized, on general sale, advertised and marketed and taxed. This worrying process has already begun in Canada. The United States has approached the issue sideways, conceding states’ rights in a way that would have delighted the Confederates.

The United Kingdom has taken a similar route: It pretends to maintain the law and, when asked, insists it has no plans to change it. But the police and the courts have gradually ceased to enforce it, so that it is now impossible to stroll through central London without nosing the reek of marijuana. Europe has gone the same way, with minor variations. Among the free law-governed nations, only Japan and South Korea still actively and effectively enforce their drug possession laws, and benefit greatly from it. But how long can they hold out?

The legalization campaigners are working like termites to undo the 1961 U.N. Convention that is the basis of most national laws against narcotics, using all the money and dishonesty at their command. They have plenty of both. So, besides the two disastrous, irrevocably legal poisons of alcohol and tobacco, we shall before long have a third—and probably a fourth and fifth not long afterward. If marijuana is legal, how will we keep cocaine and ecstasy illegal for long? Next will come heroin and LSD.

One reason for the default in favor of legalization and non-enforcement is the false association made by so many between marijuana and liberty. The belief that a dangerous, stupefying drug is an element of human liberty has taken hold of two, perhaps three generations. They should know better. Aldous Huxley warned in his much-cited but infrequently read dystopian novel Brave New World that modern men, appalled by the disasters of war and social conflict, would embrace a world where thinking and knowledge were obsolete and pleasure and contentment were the aims of a short life begun in a test-tube and ended by euthanasia. He predicted that they would drug themselves and one another to banish the pains of real life, and—worst of all—come to love their own servitude. In one terrible scene, the authorities spray protesting low-caste workers with the pleasure drug soma, and the workers end up hugging one another and smiling vaguely before returning to their drudgery. (Soma, unlike its real-life modern equivalents, is described as harmless, something easier to achieve in fiction than in reality.) What ruler of a squalid, wasteful, unfair, and ugly society such as ours would not prefer a stupefied, flaccid population to an angry one? Yet somehow, the freedom to stupefy oneself is held up quite seriously by educated people as the equal of the freedoms of thought, speech, and assembly. This is the way the world ends, with a joint, a bong, and a simper.

Whatever was wrong with my intense little segment of the 1960s revolutionary generation (and plenty was wrong with it), we believed that when we saw injustice we should fight it, not dope ourselves into a state of mind where it no longer mattered. But my tiny strand of puritan Bolsheviks was long ago absorbed into a giggling mass of cultural revolutionaries, who scrawled “Sex, Drugs, and Rock and Roll” on their banners instead of “Liberty, Equality, and Fraternity,” or even “Workers of All Lands, Unite!”

While Berenson’s facts are devastating, his own response to the crisis is feeble. He opposes marijuana legalization—and what intelligent person does not? He babbles of education and warning our children. But he declares that “decriminalization is a reasonable compromise.” Actually, it is not. It cannot be sustained. If matters are left as they are, legalization—first de facto and then de jure—will follow, because there will be no impetus to resist it. Unless the law decisively disapproves of and discourages the actual use of the drug, it is neither morally consistent nor practically effective.

The global drug trade would be nowhere without the dollars handed over to it by millions of individuals who are the end-users. We search for Mr. Big and never catch him. But we ignore or even indulge Mr. Small, regarding him as a victim, when in truth he keeps the whole thing going. In the end, the logic leads relentlessly to the stern prosecution and deterrent punishment of individual users. It is because I recognize this grim necessity that I remain a pariah. It is because he doesn’t that Alex Berenson is still just about acceptable in the part of the Western world that believes marijuana is a torch of ­freedom. 

Peter Hitchens is a columnist for The Mail on Sunday.

Source:  https://www.firstthings.com/article/2019/05/reefer-sadness

DRP0013

 1.Aims Cannabis Skunk Sense (also known as CanSS Ltd) provides straight-forward facts and research-based advice on cannabis. We raise awareness of the continued and growing dangers to children, teenagers and their families of cannabis use.

2.We provide educational materials and information for community groups, schools, colleges and universities; and guidance to wide range of professions, Parliament and the general public – with a strong message of prevention not harm reduction.

3.The Inquiry document says: ‘Government’s stated intention in its 2017 drug strategy is to reduce all illicit and other harmful drug use…….’

4.Missing from this Inquiry document is the following 2017 Strategy statement: ‘preventing people – particularly young people – from becoming drug users in the first place’. Prevention should be first and foremost in any statement as well as in the minds of us all. FRANK was mentioned just once in this strategy; ‘develop our Talk to FRANK service so that it remains a trusted and credible source of information and advice for young people and concerned others’. This claim will be challenged in this report.

5.If prevention (pre-event) were to be successful, there would be little need for a policy of reducing harmful use. Unfortunately, for fifteen or sixteen years now, prevention has taken a back seat.

6.In 1995 Prime Minister John Major’s government produced ‘Tackling Drugs Together’ saying, ‘The new programme strengthens our efforts to reduce the demand for illegal drugs through prevention, education and treatment’.

7.Objectives included: ‘to discourage young people from taking drugs’ and to ensure that schools offer effective programmes of drug education, giving pupils the facts, warning them of risks, and helping them to develop the skills and attitudes to resist drug use – all good common sense.

8.On harm reduction, the government said, ‘The ultimate goal is to ensure people do not take drugs in the first place, but if they do, they should be helped to become and remain drug-free. Abstinence is the ultimate goal and harm reduction should be a means to that end, not an end in itself’.

9.In 1998 the Second National Plan for 2001-2, ‘Tackling Drugs to Build a Better Britain’ was published. Although prevention was still the aim, the phrase ‘informed choice’ appeared, the downhill slide from prevention had started.

10.The` Updated Strategy in 2002 contained the first high-profile mention of ‘Harm Minimisation (Reduction)’. David Blunkett in the Foreword said, ‘Prevention, education, harm minimisation, treatment and effective policing are our most powerful tools in dealing with drugs’.

Some bizarre statements appeared, e.g.: ‘To reduce the proportion of people under 25 reporting use of illegal drugs in the last month and previous year substantially’. Is  infrequent use of drugs acceptable?

In October 2002 at a European Drugs Conference, Ashford, Kent, Bob Ainsworth, drugs spokesman for the Labour government, said that harm reduction was being moved to the centre of their strategy. Prevention was abandoned, ‘informed choice’ and ‘harm reduction’ ruled.

The official government website for information on drugs is FRANK set up in 2003. It continued with the harm reduction policy of the Labour Government.

From the beginning, FRANK was heavily criticised. The Centre for Social Justice (CSJ), founded by Iain Duncan-Smith MP in 2004, consistently criticised FRANK for being ill-informed, ineffective, inappropriate and shamefully inadequate, whilst citing a survey conducted by national treatment provider Addaction who found that only one in ten children would call the FRANK helpline to talk about drugs. Quite recently, when asked about sources where they had obtained helpful information about alcohol or smoking cigarettes, young people put FRANK at the bottom.

The CSJ recommended that FRANK be scrapped, and an effective replacement programme developed to inform young people about the dangers of drug and alcohol abuse based on prevention rather than harm reduction.

The IHRA (International Harm Reduction Alliance) gives the following definition of harm reduction:

Harm reduction refers to policies, programmes and practices that aim to minimise negative health, social and legal impacts associated with drug use, drug policies and drug laws. Harm reduction is grounded in justice and human rights – it focuses on positive change and on working with people without judgement, coercion, discrimination, or requiring that they stop using drugs as a precondition of support.   

The use of Harm reduction instead of Prevention is tantamount to condoning drug use – a criminal activity. The legitimate place for harm reduction is with ‘known users’ on a one to one basis as part of a treatment programme to wean them off completely and attain abstinence in a safer manner than abrupt stoppage which can be very dangerous. One example of this is to inhale the fumes of heroin rather than injection, thus avoiding blood-borne diseases such as AIDS, hepatitis and septicaemia.

An opioid substitute drug for heroin addiction, methadone has the advantage of being taken orally and only once/day. As the dosage is reduced, abstinence will be attained more safely. However, methadone users are often ‘parked’ for months on this highly addictive drug without proper supervision or monitoring. In 2008 in Edinburgh, more addicts died of methadone than heroin.

Harm reduction is a green light. If children are encouraged to use drugs by being given tips on how to use them more safely, many will do it. The son of a friend told his mother. ‘It’s OK we go on to the FRANK website and find out how to take skunk safely by cutting our use and inhaling less deeply’. He is now psychotic!

Prevention works. Between 1997 and 1991 America saw drug use numbers plummet from 23 to 14 million, cocaine and cannabis use halved, daily cannabis use dropped by 75%.

In 2005, Jonathan Akwue of In-Volve writing in Drink and Drugs News, criticised the campaign for lacking authenticity; its ill-judged attempts at humour which try to engage with youth culture; and diluting the truth to accommodate more socially acceptable messages.

The conservatives regained power under David Cameron. FRANK did not change.

In 2005, Mr Iain Duncan Smith again criticised FRANK, saying “Drugs education programmes, such as Talk to FRANK, have failed on prevention and intervention, instead progressively focussing on harm reduction and risk minimisation, which can be counter-productive”

In 2011 it was announced FRANK would be re-launched and the team commissioned ‘A Summary of Health Harms of Drugs’ from The John Moore’s University Liverpool, a hotbed of harm reduction. A psychiatrist from The FRANK Team was involved. Their section on cannabis is totally inadequate, out of date, no recognition of deaths, brain shrinkage, violence, homicides, suicides, the huge increase of strength of THC etc. Professor Sir Robin Murray’s research on mental illness (2009) and the discovery that CBD is virtually absent from skunk are of vital importance.

Many worrying papers have been written since, especially about brain development, all of which are ignored.  CanSS met with the FRANK team prior to their re-launch in 2011 where it was agreed that the cannabis section would, with their assistance, be re-written. All but two very small points were ignored, one about driving after taking alcohol with cannabis and the effect on exam results. The harm reduction advice about cannabis was removed at the request of CanSS.

Scientific evidence detailing FRANK’s inaccuracies was given to the Government by CanSS and other drug experts over the years – all of it ignored. Complaints and oral evidence were submitted to the HASC in April and September 2012 and the Education Select Committee in 2014. Government drugs spokesmen have also been contacted with concerns about FRANK.

As the official government source of information on drugs for the UK public, the FRANK site must be regularly updated and contain the many new accurate findings from current scientific research. The public is owed a duty of care and protection from the harm of drugs, especially cannabis, the most commonly used.

The following list contains some of the glaring omissions and vital details from the FRANK website:

Deaths from cancers except lung, road fatalities, heart attacks/strokes, violent crime, homicides, suicides. Tobacco doesn’t cause immediate deaths either.

Alcohol with cannabis can be fatal. An alcohol overdose can be avoided by vomiting but cannabis suppresses the vomiting reflex.

Cases of severe poisoning in the USA in toddlers are increasing, mostly due to ‘edibles’ left within reach. Accidental ingestion by children should be highlighted.

Hyperemesis (violent vomiting) is on the increase.

Abnormally high levels of dopamine in the brain cause psychosis (the first paper on this was written in 1845) and schizophrenia, especially in those with genetic vulnerabilities, causing violence, homicides and suicides. Skunk-induced schizophrenia costs the country around £2 billion/year to treat.

Young people should understand how THC damps down the activities of the whole brain by suppressing the chemical messages for several weeks. It is fat soluble and remains in the cells. Messages to the hippocampus (learning and memory) fail to reach its cells, some die, causing permanent brain damage. IQ points are lost. Few children using cannabis even occasionally will achieve their full potential.

Serotonin is depleted, causing depression and suicides. The huge increase in the strength of THC in cannabis due to the prevalence of skunk (anything from 16% to over 20%) and the almost total lack of CBD is ignored as is the gateway theory, medical cannabis, passive smoking and lower bone mineral density, bronchitis, emphysema and COPD.

They need to be taught that there is reduced ability to process information, self-criticise and think logically. Users lack attention and concentration, can’t find words, plan or achieve routines, have fixed opinions, whilst constantly feeling lonely and misunderstood. They should know of the risk of miscarriages and ectopic pregnancies.

Amazingly, the fact THC damages our DNA is virtually unknown among the public. In the 1990s, scientists found new cells being made in the adult body (white blood, sperm and foetal cells), suffered premature ‘apoptosis’ (programmed cell death) so were fewer in number. Impotence, infertility and suppressed immune systems were reported.  This is important.

In 2016 an Australian paper discovered THC badly interferes with cell division i.e. where chromosomes replicate to form new cells. They fail to segregate properly causing numerous mutations as chromosomes shatter and randomly rejoin.  Many cells die (about 50% of fertilized eggs (zygotes). Any affected developing foetus will suffer damage. Resultant foetal defects include gastroschisis (babies born with intestines outside the body), now rising in areas of legalisation, anencephaly (absence of brain parts) and shortened limbs (boys are about 4 inches shorter). Oncogenes (cancer-causing) can be switched on. Bladder, testicle and childhood cancers like neuroblastoma have all been reported. The DNA in mitochondria (energy producers in cells) can also be damaged.

Parliament controls the drug laws, so why are the police able to decide for themselves how to deal with cannabis possession?

Proof of the liberalisation of the law on cannabis possession appeared in the new Police Crime Harm Index in April 2016, where it appeared 2^nd bottom of the list of priorities. In the following November it fell to the bottom. Class ‘A’ drug possession was immediately above. Possession has clearly become a very low priority. In 2015, Durham Police decided they would no longer prosecute those smoking the drug and growing it ‘for their own use’. Instead, officers will issue a warning or a caution. Then Durham Chief Constable Mike Barton announced that his force will stop prosecuting all drug addicts from December 2017 and plans to use police money to give free heroin to addicts to inject themselves twice a day in a supervised ‘shooting gallery’.  This surely constitutes dealing. The police can it seems, alter and ‘soften’ laws at will. 

Several weeks ago, I happened to check the FRANK website. Quietly, stealthily and without fanfare, a new version had appeared – completely changed. Absent were the patronising videos, games and jokes. Left were A to Z of Drugs, News, Help and Advice (e.g. local harm reduction information) and Contact.

There is poor grammar, i.e. ‘are’ instead of ‘is’ and ‘effect’ where it should be ‘affect’. Mistakes like these do not enhance its credibility.

The drug information is still inadequate with scant essential detail, little explanation and still out of date. This is especially true of cannabis. THC can stay in the brain for many weeks – still sending out its damping-down signals.

What shocked me though were the following:

Our organisation recently received an email about a call to FRANK requesting advice. A friend, a user who also encouraged others to use as well, had lied in a court case where her drug use was a significant factor. He contacted FRANK about her disregard for the law for a substance that was illegal. The advisor raised his voice whilst stating the friend has the right to do what she wants in her own home and mocked him about calling the police. He was shocked and upset by the response.

Ecstasy – Physical health risks

• Because the strength of ecstasy pills are so unpredictable, if you do decide to take ecstasy, you should start by taking half or even a quarter of the pill and then wait for the effects to kick in before taking anymore – you may find that this is enough.
• If you’re taking MDMA, start by dabbing a small amount of powder only, then wait for the effects to kick in.
• Users should sip no more than a pint of water or non-alcoholic drink every hour.

The ‘NEWS’ consisted of 8 pictures with text. In 2 of the 8 items, opportunity is taken to give more ecstasy harm reduction advice. One is titled, ‘Heading out this weekend with Mandy or Molly?’ This is blatant normalisation. The others aren’t ‘news’ items either, but more information about problems.

The section on each drug entitled, ‘Worried about drug x’ mostly consists of giving FRANK’s number. ‘If you are worried about your use, you can call FRANK on 0300 1236600 for friendly, confidential advice’. Any perceptions that FRANK is anything but a Harm Reduction advice site are dispelled completely.

Mentor International is a highly respected worldwide Prevention Charity.  Government-funded Mentor UK is in charge of school drug-education with their programme, ADEPIS (Alcohol and Drug Education and Prevention Information Service). Mentor UK masquerades as a ‘Prevention’ charity but practices ‘Harm Reduction’ and has done so from its inception in 1998. A founding member, Lord Benjamin Mancroft, is currently prominent in the APPG: Drug Policy Reform, partly funded by legaliser George Soros’s Open Society Foundation.

Professor Harry Sumnall of John Moores University Liverpool, a trustee on Mentor UK’s board, signed a ‘Legalisation’ letter in The Telegraph 23^rd November 2016 along with the university, Professor David Nutt, The Beckley Foundation, Nick Clegg, Peter Lilley, Transform, Volte-face and other well-known legalisation advocates. Eric Carlin, former Mentor UK CEO (2000-2009), is now a member of Professor David Nutt’s Independent Scientific Committee on Drugs (ISCD). At a July 2008 conference in Vienna, he said “we are not about preventing drug use, we are about preventing harmful drug use”.

Examples of their activities:

The ‘Street Talk’ programme, funded by the Home Office, carried out by the charities Mentor UK and Addaction and completed in March 2012 was aimed to help vulnerable young people aged 10 – 19, to reduce or stop alcohol and drug misuse. Following the intervention, the majority of young people demonstrated a positive intention to change behaviour as follows: “I am confident that I know more about drugs and alcohol and can use them more safely in the future” – 70% agreed, 7% disagreed’.

 Two CanSS members attended a Mentor UK meeting on 7^th January 2014 at Kent University, where Professor Alex Stevens, a sociology professor favouring the opening of a ‘coffee shop’ in Kent and supporting ‘grow your own’ was the main speaker. The audience consisted mainly of young primary school teachers. He became increasingly irritated as CanSS challenged his views, becoming incandescent when told knowledge of drug harms is the most important factor in drug education. The only mention of illegality (by CanSS) was met by mirth!

In a Mentor UK project ‘Safer at school’ (2013), the greatest number of requests from pupils, by 5 to 6 times, were: – effects of drugs, side-effects, what drugs do to your body and consequences. Clearly it had been ignored. Coggans 2003 said that, ‘the life skills elements used by Mentor UK may actually be less important than changing knowledge, attitudes and norms by high quality interactive learning’.

Paul Tuohy, the Director of Mentor UK in February 2013 emailed CanSS, ‘Harm reduction approaches are proven and should be part of the armoury for prevention……..there are many young people harming their life chances who are already using and need encouragement to stop, or where they won’t, to use more safely’.

In 2015 Mentor incorporated CAYT (Centre for Analysis of Youth Transitions) with their ‘The Climate Schools programmes’. Expected Outcomes: ‘To show that alcohol and drug prevention programmes, which are based on a harm minimisation approach and delivered through the internet, can offer a user-friendly, curriculum-based and commercially-attractive teaching method’.

In November 2016, Angelus and Mentor UK merged, ‘The Mentor-Angelus merger gives us the opportunity to reach a wider audience through the delivery of harm-prevention programs that informs young people of the harms associated with illicit and NPS drug-taking, to help support them in making conscientious healthy choices in the future’.

The under-developed brains in young people are quite incapable of making reasoned choices. Nor should they. Drug-taking is illegal.

Michael O’Toole (CEO 2014 –2018) said in an ACMD Briefing paper.

‘Harm reduction may be considered a form of selective prevention – reducing frequency of use or supporting a narrowing range of drugs used’. “It is possible to reduce adverse long-term health and social outcomes through prevention without necessarily abstaining from drugs”. 

It is a puzzle that any organisation, including the Government, can condone drug-taking, an illegal activity, either by testing drugs or dishing out harm reduction advice, without being charged with ‘aiding and abetting’ a crime.

Mary Brett, Chair CanSS and Lucy Dawe,Administrator CanSS www.cannabisskunksense.co.uk    

Source: http://data.parliament.uk/writtenevidence/committeeevidence.svc/evidencedocument/health-and-social-care-committee/drugs-policy/written/97965.html March 2019

— Effect on sperm quality, testicular function worse than cigarettes

CHICAGO — Men who smoked marijuana had significantly degraded sperm quality and testicular function, worse than tobacco users and comparable to men with diagnosed infertility, according to a long-term Brazilian study.

As compared with smokers, marijuana users had lower median values for sperm concentration, motility, and morphology (P<0.01). Marijuana use also was associated with reduced testicular volume and an increased rate of nonobstructive azoospermia, clinical features often found in male infertility.

Marijuana’s deleterious effects on reproductive parameters resulted from increased production of reactive oxygen species (ROS), as seminal ROS concentrations were 20 times higher in marijuana users as compared with smokers, reported Jorge Hallak, MD, of the University of Sao Paulo, at the American Urological Association (AUA )annual meeting.

“Overall, the marijuana group had semen quality equivalent to the infertile group, with the exception of higher ROS and DNA damage than infertile men,” Hallak said during an AUA press briefing. “DNA damage is higher in all groups (marijuana users, smokers, and infertile men) as compared to controls, but higher levels were found in the marijuana group and infertile men. Basic semen parameters are not sufficient to identify changes of magnitude in sperm cell function.”

A second study summarized at the press briefing provided the first reported evidence of an association between marijuana use and development of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).

A recent international study showed a consistent and statistically significant decline in sperm quality (count and motility) over the past 40 years. The explanation for the decline remains elusive, but multiple factors have been proposed: environmental exposures, poor nutrition, genetics, and social/behavioral factors.

Over the past 2 decades, technologic advances allowed more detailed examination of sperm. Showed that sperm are highly vulnerable to oxidative stress, which has been implicated in a multitude of major human diseases and disorders. Subfertility and infertility almost almost always arise as a consequence of oxidative stress, said Hallak.

The rationale for evaluating marijuana’s effect on male fertility parameters included a lack of information on the topic and the worldwide use of the drug. With an estimated 200 million users worldwide, marijuana is the most widely used psychoactive drug, including more than 20 million regular users in the U.S.

Since 2000, Hallak and colleagues have studied the effects of marijuana and tobacco on spermatozoa and testicular function and relationships with male infertility, hypogonadism, and sexual dysfunction. Each study participant has two comprehensive semen analyses that go well beyond usual lab assessments and include ROS, sperm DNA integrity, creatinine kinase activity, and antisperm antibodies.

Unlike many prior studies, enrollment was limited to users of cannabis and excluded use of cannabinoid-containing products. The study population comprised 125 men with diagnosed infertility, 144 tobacco smokers, 74 marijuana users, and a control group of 279 men (prevasectomy with no clinical factors for testicular dysfunction).

Current marijuana use was ascertained by self-report at the time of enrollment. Median age at first use of marijuana was 18.6, and median duration of marijuana use was 8 years.

Clinical characteristics of the infertile men included increased levels of prolactin; decreased sperm concentration, motility, and morphology; and increased seminal pH and ROS. Tobacco smokers had decreased follicle-stimulating hormone, luteinizing hormone, and prolactin; decreased testicular volume; and decreased seminal volume.

Marijuana users had a significantly lower median estradiol level (10.04 ng/dL) as compared with all the other groups (P<0.001). Marijuana use was associated with the highest median seminal ROS: 14.31 x 104 cpm/20 x 10⁶ versus 5.66 for infertile men, 0.70 for smokers, and 0.68 for the fertile control group. Hallak noted that marijuana induces production of intracellular ROS whereas tobacco smoke creates extracellular oxidative stress.

The study of marijuana use and BPH/LUTS included 20,548 men (age >45) who had prescriptions for finasteride and or a super-selective alpha blocker during the period from January 2011 to October 2018. The primary objective was to identify factors significantly associated with BPH/LUTS, said Granville Lloyd, MD, of the University of Colorado Anschutz School of Medicine in Aurora.

A multivariable analysis identified marijuana use as a statistically significant player in the development of BPH/LUTS (odds ratio 1.253, P<0.001). Other significant predictors were depression (OR 2.015), erectile dysfunction (OR 1.847), metabolic syndrome/obesity (OR 1.586), hypertension (OR 1.576), hypogonadism (OR 1.392), and diabetes (OR 1.280, P<0.001 for all). Alcohol use did not have a significant association with BPH/LUTS (OR 0.982).

Noting that BPH/LUTS etiology is poorly understood, Lloyd said, “From this analysis we can conclude that BPH is associated with systemic diseases, depression, and marijuana use but not alcohol.”

“Men who use marijuana are more likely to be treated for BPH,” he stated. “This is a novel finding. Cannabinoids are pharmacologically active and influence voiding, which raises the question of whether marijuana is a risk factor or self-treatment?”

Source: Studies: Weed Degrades Sperm, Spurs LUTS | MedPage Today May 2019

It is not all that long since people seriously tried to pretend that cigarettes were safe. Most of them were motivated by greed, and by fear that the truth would destroy their profits.

Everyone now agrees that cigarettes cause lung cancer and many other diseases. But we forget the struggle that doctors and scientists had to fight, against Big Tobacco, to get this accepted.

Sir Richard Doll and Sir Austin Bradford-Hill established in 1950 that there was a clear link between smoking and cancer. A wider study in 1954 absolutely confirmed this.

Yet such was the power and wealth of the tobacco giants that it was decades before anything serious was done to discourage smoking. It was not until 1971 that the first feeble warning was placed on cigarette packets in this country.

As late as 1962, the cigarette-makers were still pretending there hadn’t been enough research, and even that tobacco was good for you, claiming ‘smoking has pharmacological and psychological effects that are of real value to smokers’.

A Tory MP, Ted Leather, denounced the doctors’ warnings as ‘unscientific tosh’ and ‘hysterical nonsense’. Lung cancer was blamed on air pollution. The prominent journalist Chapman Pincher proclaimed ‘cigarette risks are being exaggerated’. It was seriously argued that restrictions on smoking were an attack on liberty.

I’d guess that many who made such claims lived to regret, bitterly and with some embarrassment, their part in covering up a terrible danger. Those who listened to them died, early and often horribly. They are still dying now, in cancer wards up and down the country.

Earlier, firmer action would have saved them and their families from much grief. Those tobacco apologists all have their parallels now.

I know, but will not name here, drug lobbyists, a Tory MP and several prominent journalists, who make the same excuses for marijuana, just as the evidence of its grave dangers piles up. They claim the evidence against it is exaggerated. They claim it has medical benefits. They claim its effects are caused by something else. May God forgive them. I cannot.

Our society, learning nothing from the tobacco disaster, has for years been appallingly complacent about this terribly dangerous drug, whose effect on the brains and minds of its users can be utterly devastating. Knowledge of its dangers does not show up in statistics which pay little attention to the sort of damage it does.

The victims of marijuana seldom die (though they increasingly frequently kill others, in mad car crashes and violent crime).

School failure, delinquency, delusional behaviour, persecution mania, young lives wholly blighted and continued only thanks to a devastating cocktails of antipsychotic drugs, do not register much in NHS figures. Nor do the special miseries of the families of these people, compelled to care, for life, for a husk of the person they once knew and had hopes for, and still love. Such families keep their grief to themselves. But there are many of them.

Look, I am right about this. But it is no good being right if you are not believed. I and my allies are roughly where the doctors who warned against lung cancer were in the mid-1950s. The evidence keeps on coming. Last week’s report linking marijuana use to depression and suicidal feelings among the young is just the latest in a great mountain of such studies. But the popular culture continues to act as if there’s nothing to worry about.

It is now seven years since I published a book which pointed out the truth – that the police and courts have given up prosecuting the major crime of marijuana possession. Back in 2012 I was denounced, snubbed, sneered at and told by distinguished academics that I was wrong and that there was a stern regime of cruel prohibition.

Now everybody recognises that what I said seven years ago is absolutely true. It is hard not to do so when so much of our country openly stinks of marijuana. Even if the Commissioner of the Metropolitan Police, Cressida Dick, cannot smell it, the rest of us can.

Sooner than seven years from now, I suspect that the connection between marijuana and severe mental illness will also be widely understood and accepted. But will it be too late?

Today’s Big Dope lobby wants to silence warnings about the dangers of marijuana until they have it legalised, and we can’t go back. They are like the Big Tobacco of the 1950s, a cynical greed campaign prepared to cause misery to others in the pursuit of riches.

This is the reason for its busy Trojan Horse operation to portray marijuana as a medicine, a claim for which there is very little evidence. And in any case, what use would a medicine be whose users risked irreversible mental illness?

Thalidomide was wonderful at treating morning sickness. But what does that matter compared with its terrible side effects?

Be on your guard. Make sure your MP isn’t fooled by Big Dope propaganda. Write to your MP when you see reports of crimes whose perpetrators were cannabis smokers. Your local papers will be full of them, if you look. Ask your MP to read the many reports linking this drug with mental illness.

And don’t be fooled. All of us sympathise with the mothers of very sick children who seek remedies for them. But beware of the shadowy figures who often stand behind such stories, and who use this suffering to promote a nasty cause.

It’s a race against time. If we lose it, the suffering which follows will be at least as bad as the suffering caused by cigarettes, and probably far worse.

Peter Hitchens  Mail on Sunday  

Source: Cigarettes are healthy! (And if you believe that, you’ll fall for Big Dope’s marijuana propaganda, too) – Mail Online – Peter Hitchens blog (mailonsunday.co.uk) February 2019

DEA says Houston is both a big market for synthetic pot and a major source

More than 1 million packets of a dangerous, unpredictable new breed of drug were seized in the Houston area by the DEA in the past two years, yet criminal charges are rare for those who make, sell or use them.

The packets, sold as potpourri or incense, are among the more popular brands of so-called synthetic marijuana taking center stage in a new front in the war on drugs.

Source: https://www.houstonchronicle.com/news/investigations/article/Houston-gains-key-role-in-synthetic-marijuana-5024607.php  November 2013

Kevin Sabet was a drug control policy adviser in the White House for both Republicans and Democrats

When most people talk about Canada’s impending legalization of marijuana, they talk about the future. When Kevin Sabet talks about it, he worries about history repeating. 

“There are huge misconceptions, I often feel like we’re living in 1918, not 2018,” he said.” When I say 1918, I mean 1918 for tobacco when everyone thought that smoking cigarettes was no problem and we had a new industry that was just starting.”

In 1918, soldiers returning home from the trenches of the First World War brought cigarettes home with them and unwittingly sowed the seeds of one of 20th century’s biggest health epidemics. 

“We hadn’t had tobacco related deaths before the 20th century because we hadn’t had a lot of cigarettes, which actually gave us the most deadly form of tobacco we’ve ever seen. I feel like we’re like that with marijuana.”

A former drug control policy adviser to the White House under both the Democrats and Republicans, Sabet is the President and CEO of Smart Approaches to Marijuana, a public health organization opposed to marijuana legalization and commercialization in the United States. 

He said the sudden about-face by Ontario’s newly-elected Progressive Conservative government away from a public monopoly on marijuana sales to a mixed public-private is “a really bad move.” 

“When I see the government monopoly being tossed out the window in favour of a private program that really puts private profit over public health.. I worry about that,” he said. “I think it’s a really bad move.” 

“They are moving from a government monopoly to private retail and that’s going to open the door to all the marketing and promotion and normalization that already is a huge problem for our already legal drugs.”

“We’ve seen how that turned out for pharmaceuticals like opiates, which are highly dangerous and we’ve seen how that turned out for tobacco and alcohol.”

Big investors lining up to cash-in on pot

Source: Ontario’s new retail pot plan ‘puts profit over public health’ says former Obama drug adviser | CBC News August 2018

• Teenagers who smoke have thicker matter in certain parts of their brains
• This was found in areas involved with emotions, memory, fear and panic
• Adolescent brains are typically thinning and being refined during this period
• Experts said ‘most people would assume one or two joints would have no impact’

Just one or two joints is enough to change the structure of a teenager’s brain, scientists have warned.

And the drug could cause changes affecting how likely they are to suffer from anxiety or panic, according to a study.

Researchers found 14-year-old girls and boys exposed to THC – the psychoactive chemical in cannabis – had a greater volume of grey matter in their brains.    

This means the tissue in certain areas is thicker, and it was found to be in the same areas as the receptors which marijuana affects.

Experts said thickening of brain tissue is the opposite of what usually happens during puberty, when teenagers’ brain matter gets thinner and more refined.

Researchers did scans of teenagers’ brains and discovered those who had been exposed to small amounts of marijuana (top row) had thicker regions of the brain (indicated by more orange and yellow tissue) than those who had never smoked cannabis (bottom row)

Researchers from the University of Vermont scanned the brains of teenagers from England, Ireland, France and Germany to study marijuana’s effects. 

They found differences in the volume of grey matter in the amygdala and the hippocampus.

These sections are involved with emotions, fear, memory development and spatial skills – changes to them suggests smoking cannabis could affect these faculties.    

Scientists said theirs is the first evidence to suggest structural brain changes and cognitive effects of just one or two uses of cannabis in young teenagers.

And it suggests as teenagers brains are still developing, they may be particularly vulnerable to the effects of THC.

THC, full name tetrahydrocannabinol, is the chemical in marijuana which makes people high and is what makes it illegal in the UK. 

‘Consuming just one or two joints seems to change grey matter volumes in young adolescents,’ said study author Professor Dr Hugh Garavan.

‘The implication is that this is potentially a consequence of cannabis use. You’re changing your brain with just one or two joints.

‘Most people would likely assume that one or two joints would have no impact on the brain.’

What changes the increased brain volume directly causes is unclear, but the researchers said it is important to understand cannabis’s effects in detail.

This is especially so in the US, where more states are legalising the drug and a view of it being harmless is spreading, they said.

Professor Garavan said cannabis use appears to produce the opposite effect on brain matter of what usually happens during puberty. 

He said a typical adolescent brain undergoes a ‘pruning’ process in which  it gets thinner, rather than thicker, as it refines its connections. 

‘One possibility is they’ve actually disrupted that pruning process,’ he said. 

Previous studies have focused on heavy marijuana users later in life and compared them against non-users. 

Few have looked at the effects of the first few uses of a drug.

Another of the study’s authors, Catherine Orr, now a lecturer at Swinburne University of Technology in Australia said: ‘Rates of cannabis use among adolescents are high and are increasingly concurrent with changes in the legal status of marijuana and societal attitudes regarding its use.

‘Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of THC on brain structure.’

The study, part of a long-term European project known as IMAGEN, involved 46 teenagers who used recreational marijuana once or twice by the age of 14.

They reported how many joints they had smoked and had brain scans.

It also involved 69 teenagers who used the drug at least 10 times between the ages of 14 and 16, and 69 who had not touched the drug by age 16.

Scientists also assessed them for signs of various mental disorders including ADHD, anxiety, depression and panic disorder.    

Dr Orr said: ‘Of the behavioural variables tested, only sensation seeking and agoraphobia differed between the cannabis users and controls. And these factors were not related to greater grey matter differences.’ 

The researchers said the area of the brain which cannabis interacts with is particularly important for brain development in adolescence, suggesting teenagers could be particularly affected by THC. 

Dr Orr concluded: ‘Almost 35 per cent of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects.

‘We understand very little about the earliest effects of cannabis use, however, as most research is conducted in adults with a heavy pattern of lifetime use.

‘This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence.’  

The study was published in The Journal of Neuroscience.

Source: Smoking weed just ONCE could change a teenager’s brain | Daily Mail Online January 2019

Abstract

Keywords: attention; cannabis; intellect; intrauterine; memory; perception.

Source: Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1-11 years: A systematic review – PubMed (nih.gov) November 2018

What are Marijuana Concentrates or THC Concentrates? 

A marijuana concentrate is a highly potent THC concentrated mass that is most similar in appearance to either honey or butter, which is why it is referred to or known on the street as “honey oil” or “budder.”

What Does it Look Like?

Marijuana concentrates are similar in appearance to honey or butter and are either brown or gold in color. The different forms include: hash or honey oil (a goey substance), wax or butter (soft, lip balm-like substance), and shatter (a hard, solid substance). (See photo gallery at the bottom of the article)

What are the Street Names?

710 (the word “OIL” flipped and spelled backwards), wax, ear wax, honey oil, budder, butane hash oil, butane honey oil (BHO), shatter, dabs (dabbing), black glass, and errl.

How is it Made?

One popular extraction method uses butane, a highly flammable solvent, which is put through an extraction tube filed with marijuana. The butane evaporates leaving a sticky liquid known as “wax” or “dab.” This method is dangerous because butane is a very explosive substance. There have been explosions in houses, apartment buildings and other locations where someone tried the extraction. 

How is it Used?

It’s used a few ways:

• Infusing marijuana concentrates in various food or drink products
• Smoking remains the most popular form of ingestion by use of water or oil pipes or heated in a glass bong.
• Electronic cigarettes (also known as e-cigarettes) or vaporizers. Many users of marijuana concentrates prefer the e-cigarette/vaporizer because it’s smokeless, odorless, and easy to hide or conceal. The user takes a small amount of marijuana concentrate, referred to as a “dab,” then heats the substance using the e-cigarette/vaporizer producing vapors that ensures an instant “high” effect upon the user. Using an e-cigarette/vaporizer to ingest marijuana concentrates is commonly referred to as “dabbing” or “vaping.”

What are the Effects of Using Marijuana Concentrates? 

Marijuana concentrates have a much higher level of THC. The effects of using may be more severe, both psychologically and physically. 

Sources: “Marijuana Extracts,” National Institute on Drug Abuse (NIDA); “Marijuana Concentrates,” Drugs of Abuse – DEA.

Source: What You Should Know About Marijuana Concentrates/ Honey Butane Oil | Get Smart About Drugs March 2022

An investor in a major Canadian cannabis company has had longstanding ties, including business dealings, with influential Mafia members and drug traffickers, Radio-Canada has learned.

Another investor in the same company has links with a prominent member of the Rizzutos, the powerful Montreal crime family.

In still another case, an individual managed to sell his cannabis business to one of the big players in the industry, despite his connections to drug traffickers. In return, he received shares in the company and rented out space for a cannabis grow-op.

Prime Minister Justin Trudeau’s legalization plan was supposed to cut out organized crime, but an investigation by Radio-Canada’s Enquête shows Health Canada has granted production licences to companies with individuals with links to the criminal underworld.

Enquête examined hundreds of documents as part of its investigation, including reviews conducted by Canadian securities oversight bodies. Enquête is not naming the companies or individuals involved.

For its part, Health Canada says it has not seen any cases of organized crime infiltration of more than 130 licensed cannabis producers since 2013.

To produce cannabis, those who hold certain positions in companies must first obtain a permit from Health Canada by taking a security screening.

Any past connections with individuals related to organized crime are part of the analyzed information.

Red flags raised

To secure a licence, Health Canada first checks if the individual has a criminal record.

Second, the RCMP consults police databases to review information that may indicate an applicant’s links to criminals.

Health Canada makes its final decision with the information provided by the RCMP.

The RCMP says it raised red flags on about 10 per cent of the applicants it was asked to check out in 2016 and 2017.

“It’s really criminal associations,” says Supt. Yves Goupil, who gives the example of a person “associated with individuals who have criminal records.”

In a statement, Health Canada said it can “categorically confirm” that it didn’t issue “security clearance to an individual when the RCMP provided evidence to the department that it was associated with organized crime.”

“Health Canada has found no evidence that organized crime has infiltrated one of more than 130 federally registered producers,” spokesperson Eric Morrissette said in an email.

Security checks only scratch the surface

Throughout the period in which Canada’s cannabis industry was developing, primarily for medical purposes, only individuals who directly ran the companies were required to obtain a security clearance.

This approach, says Conservative Senator Claude Carignan, demonstrates a naiveté about the workings of high-level organized crime.

“If there is someone who has a criminal record, it is not that person they will put to apply for the licence,” Carignan said. “It would be completely naive to think that.”

Last spring, Carignan and his Senate colleagues tried, unsuccessfully, to amend Bill C-45 on the legalization of cannabis in order to demand more transparency from companies entering the industry.

Several companies have opaque and complex structures.

“You never see who the real licence holders are,” said lawyer and tax expert Marwah Rizqy, who raised the issue before a Senate committee last spring and has since been elected Liberal MNA for the Quebec riding of Saint-Laurent.

The black hole of trusts

It’s not uncommon for cannabis companies to be funded through family trusts.

Originally designed for estate and tax planning, trusts are an ideal way to hide individuals with interests in a business, said Marie-Pierre Allard, who studies tax policy at the Université de Sherbrooke.

“The beneficiaries of the trust are not disclosed publicly. It’s anonymous,” she said, adding that it is “one of the great vulnerabilities of the Canadian legal system.”

“If we want to eliminate the Mafia cannabis market, we cannot allow them to use tax havens or trusts to enter indirectly through the back door,” Carignan said.

A report by the federal Department of Finance and several international organizations identifies trusts as one of the vehicles most at risk for money-laundering in Canada.

In a Senate appearance last April, Rizqy suggested refusing to grant production licences to companies financed through trusts.

“Maybe it would be wise to deny the licence outright because you are not able to unequivocally establish that the security clearance is really valid,” said Rizqy.

The recommendation was not accepted. The federal cannabis legislation adopted this summer, however, did include more extensive background checks into individuals who back cannabis companies.

Too many requirements for the cannabis industry?

Carignan has faced criticism for his efforts to make cannabis companies more transparent.

Line Beauchesne, a criminologist at the University of Ottawa, believes Health Canada’s investigations are adequate and consistent with the government’s desire to ensure the quality of the product and to prevent smuggling.

“Why especially for the cannabis industry?” Beauchesne asked.

If there were to be new rules of transparency, “all industries moving into Canada” should be affected, she said.

She acknowledged, however, that Health Canada “is absolutely not equipped to conduct financial investigations.”

Its traditional role is to ensure a product meets certain standards.

“Health Canada’s job is to make sure that when I eat cheese, it’s cheese. When it’s eggs, it’s eggs. And when [it comes to] cannabis, it’s cannabis.”

The limits of police investigations

The number of audits to be conducted in the cannabis industry is so great investigators have to make choices, said the RCMP’s Goupil.

The work of police is complicated considerably when the sources of financing for businesses come from abroad, including from tax havens.

“Technically, there is nothing illegal there. But it’s hard for [the RCMP] and for Health Canada to go out and check in those countries,” he said.

“Often, it’s going to be the janitor who will sign the company documents or a law firm in country X. At some point, we cannot do the research. It’s a lot of investment, a lot of time, a lot of money,” Goupil said.

“We cannot have a fully bulletproof system. If organized crime has an opportunity to make a profit, it will exploit it. “

Tax havens are not the only barrier to police work. Secrecy also exists in some companies in Canada.

“We need to use other more advanced techniques such as physical surveillance and wiretapping that will help us identify who is behind the company and who operates it,” he said.

These survey techniques, however, require considerable resources and cannot be deployed for all cannabis companies.

“We cannot afford it.”

Source: Licensed cannabis growers have ties to organized crime, Enquête investigation finds | CBC News November 2018

Radula complanata, a cannabinoid moss. Henri Koskinen/Shutterstock

Most of us know that the cannabis plant produces compounds that react with the human body. That’s because we have our own system that makes similar compounds, cannabinoids, that have a wide range of actions from appetite control to immune function. Cannabis contains a cannabinoid called THC that interacts with the brain, resulting in euphoria and relaxation, as well as increased hunger and anxiety. It was long thought that there was no other natural source of cannabinoids – and along with a long list of supposed medical uses the mythical power of cannabis, and the psychoactive properties of THC, has grown.

But as it turned out, another plant contains something similar: a compound that has the structural hallmarks for it to act on the brain in a similar way to THC. The discovery of this lost twin, called cis-PET (perrottetinene), or PET, was tucked away in specialist chemistry journals in papers published in 1994 and 2002, with no subsequent research confirming its biological activity. But in a new study, published in Science Advances, a group of Swiss scientists have delved into the mechanism by which PET may be acting on the brain.

The particular liverwort in question, Radula, is endemic to New Zealand and Tasmania and is used as a herbal medicine by the Maori people. Preparations using this plant are also sold as a THC-like legal high on the internet.

But while similar to THC, does PET actually produce the same effects that THC does at a cellular and molecular level? Does it mimic the physiological effects? And is it different in ways that could give it therapeutic advantage or disadvantage? Some 24 years after its first discovery, the team of chemists and biochemists behind the new study have teased some of the answers out.

Their research was no mean feat. It required a new synthesis method to produce enough PET to do meaningful experiments. Once this was achieved, the researchers looked at two mirror versions of the two compounds, cis (the version found in the liverwort) and trans (a version they artificially created in the lab). In chemistry, the cis and trans terms tell us which side of the carbon chain the functional groups are (the bit of the molecule that does the work).

The researchers wanted to find out if these two versions of PET were able to interact with the two receptors found in humans that mediate the psychoactive effects of cannaboids – CB1, the receptor that produces the “high” effect from THC, and CB2 – in the same way as THC (how strongly they bound and how much is needed to produce an effect).

The researchers found intriguing similarities between the two versions in PET and THC. For both PET and THC, the trans versions (the abundant THC version found in cannabis and the lab-synthesised version found in liverwort) bound to the CB1 receptor better than the cis versions.

THC and PET side by side. Oliver Kayser

What’s interesting about this is that while the levels of cis-PET found in the liverwort plant are too low to produce the “high” effects produced by THC (hence why smoking PET won’t produce a high), it could explain why PET might still have a medicinal effect (similar to the effect produced by lower dose THC). However, any methods to extract and concentrate the liverwort compound could lead to the same problems as THC.

But what about CB2, the other cannabinoid receptor? This receptor plays a role in immune responses. Here the Swiss scientists found that the cisversions of both THC and PET bound this receptor better than the transversions. The implications of this are yet to be explored, but it again hints at a potential medicinal benefit worth exploring further.

The authors of the study then went on to test whether the binding of the CB1 receptors in the brains of mice had the same recognisable THC effects. Usually when THC binds with this receptor it produces four key effects: reduced body temperature, muscle rigidity, reduced movement and decreased sensitivity to pain. In this behavioural test, all four effects were also achieved in the mice using cis-PET, albeit in a much bigger amount.

But there was one notable difference. Inflammation in the brain is mediated by molecules called prostaglandins that can be derived from metabolic pathways involving our own body cannabinoids or plant-derived trans-THC. In contrast, the production of these mediators was reduced by cis-PET. It remains to be seen whether this is a good thing or a bad thing.

So while the study is just a start in understanding the mechanisms and effects of PET on the brain, there’s much we still don’t know. What we do know now, however, is that the levels of PET that are found in the natural liverwort plant are too low to produce the recognised effects of THC, so smoking it is unlikely to lead to a high. But it is also interesting that this compound could well have medicinal benefits without the high – one of the key reasons that THC has previously been dismissed as a medicine. Illegal trading and cultivation has confounded much meaningful clinical research, but this is changing and this new compound will add to the treasure trove of plant-derived cannabinoids that we still have much to understand.

Source: https://theconversation.com/liverwort-could-have-medicinal-benefits-of-cannabis-thc-without-the-high  Oct.24^th 2018

* Correspondence:

Albert Stuart Reece  

A leading perspectives piece in the New England Journal of Medicine recently observed the salience of assessing drug safety in children and emphasized that effects experienced in childhood can have long lasting impacts as they interfere with maturation and growth of the organism into later life.  Senior researchers from the National Institute of Drug Abuse have frequently drawn attention to the implications of adolescent cannabis exposure.  The effects of gestational exposure are even more far reaching.  These factors are given further urgency by studies showing 25% of Californian teenage mothers in California use cannabis.

Cannabis-related neuroteratology appears to clearly fall on a spectrum of deficits.

With the obvious caveats that many of the longitudinal studies of prenatal cannabis exposure (PCE) have been conducted in very different populations, that it is not easy to control for other sociodemographic factors frequently associated with drug use, and that the concentration of cannabis commonly used in the older studies was much lower, findings which together engender a fair degree of heterogeneity in the published reports, a remarkably consistent thread runs through the PCE literature.  Three major longitudinal studies have followed children exposed prenatally from white middle class Ottawa from the late 1970’s; from predominantly African-American Pittsburgh from 1982; and from the Netherlands from 2001.  Reductions in birth weight of 200-300g, slightly smaller head circumferences (2.8mm), and body length are reported in weekly users with several studies reporting dose-response effects.

In terms of neurobehavioural functioning increased neonatal startle response were seen, with specific cognitive defects in grade school, increased impulsivity, hyperactivity and depression at age 10, poor school achievement, adolescent delinquency, increased violence and aggression amongst girls, increased use of tobacco and cannabis in teens, and in the early 20’s in the longest running study, deficits in short term memory, visuospatial memory and motor impulse control.  These defects have been linked with ADHD and with autism.  Microcephaly was also noted in a large Hawaiian study.  Increased neonatal startle and later cognitive defects are also seen in rodents after PCE.

These findings are clinically significant, and may assume public health significance when one notes that autism is increasing in all USA states where it is measured, paralleling rising rates of cannabis use across the country.

Two reports from C.D.C. indicate an almost doubling of the rate of anencephaly following PCE R.R.=1.9 (95%C.I. 1.1-3.2).  In the context of the foregoing findings this major datum implies that cannabis has the unusual distinction of being a neurotoxin which interferes with brain development to the point of chemically amputating the forebrain.  Hence there is clear evidence of a graded spectrum of deficits following PCE from subtle ASD- and ADHD- like neurobehavioural defects, to smaller heads, to microcephaly and to anencephaly including foetal neurological and neonatal death.

In the context of indicative epidemiology consideration of pathophysiological mechanisms is pertinent to address the Hill principles of causality.

There are numerous compelling mechanisms by which PCE can be related to subsequent teratogenic outcomes.

Importantly the cerebellum, midbrain, diencephalon and forebrain express moderate to high levels of type 1 cannabinoid receptors (CB1R) from early in gestation.

It was recently powerfully demonstrated that opposing gradients of the ligand-receptor guidance pairs slit-Roundabout (robo) and the notch ligand dll control and determine mammalian corticogenesis in diverse organisms including snakes, birds, mice and human organoids by controlling the switch for cortical neurogenesis from directly via radial glia cells to a more indirect and proliferative pathway via intermediate progenitors (Figure 1).   Cannabinoids have been shown to reverse this natural gradient for dll, and acting via a 2AG / CB2R / slit2 / Robo1 / 2AG / CB1R / JNK / ERK pathway to stimulate robo.

Neurexin-neuroligin is a trans-synaptic ligand-receptor pair which directly induces and maintains synapse formation, and has been shown to be inhibited by cannabinoids.

Axon guidance is also controlled by robo-slit and by stathmin-induced tubulin polymerization, which are sensitive to cannabinoids.

White matter disconnection is well documented following adolescent and prenatal cannabis use, and in autism, and oligodendrocytes have CB1R’s and CB2R’s.

Mitochondria possess both CB1R’s and cannabinoid signal transduction machinery and are known to be highly sensitive to cannabinoids and interact with DNA maintenance pathways by several routes.

Cannabinoids have also been shown to alter signaling via the neurotransmitters: glutamate, GABA, opioids, dopamine, serotonin and enkephalin.

Cannabinoids have demonstrated intergenerational epigenetic effects on the medium spiny neurons of the nucleus accumbens and amygdala and also on immune cells which sculpt dendritic networks and prune synapses.

Acting via CB1R, GPR55, and vanilloid type 1 receptors cannabis has been linked with arteritis with likely downstream actions on neurogenic and other stem cell niches.

Endocardial cushions also carry high levels of CB1R’s and the American Academy of Pediatrics has a position statement noting the increased incidence of Ebstein’s syndrome and ventricular septal defect (VSD) after PCE.  Both syncytiotrophoblast and placental arteries carry high concentrations of CB1R’s and abnormalities of uterine blood flow have been documented.

Cannabinoids interfere with tubulin polymerization and mitotic spindle function and thereby act as indirect genotoxins. The implication of cannabis with four inheritable cancers implies malignant teratogenicity and genotoxicity.

Colorado reports dramatic rises of total congenital anomalies, microcephaly, VSD, ASD, Down’s syndrome and chromosomal defects, all of which are relatively straightforward to quantify.

Colorado legislators have also moved to declare a state of crisis related to an autism rate presently growing by 30% 2012-2014.  Similarly in northern California a coincident hotspot of cannabis use, gastroschisis and autism has been reported.  In New Jersey 4.5% of 8 year old boys are autistic.

The above findings comprehend both positive and negative association along with multiple plausible biological pathways linking causality.

As rising rates of community cannabis use augment rising cannabis concentrations and intersect often asymptotic cannabinoid dose-response genotoxicity curves, increased clinical teratogenesis is to be expected.  Of these anomalies the neurobehavioural teratology will likely be the most common, is arguably the most costly and severe, and is also most difficult to quantify.

Are we prepared?

Source:  Paper by Albert Stuart Reese sent to Elinore.Mccance-katz@samhsa.hhs.gov  2018

Source: 2017-Cannabis-Toxic-Trend-Report.pdf (wapc.org) 2017

From a Colorado Springs Gazette Opinion

Last week marked the fifth anniversary of Colorado’s decision to sanction the world’s first anything-goes commercial pot trade.

Five years later, we remain an embarrassing cautionary tale.

Visitors to Colorado remark about a new agricultural smell, the wafting odor of pot as they drive near warehouse grow operations along Denver freeways. Residential neighborhoods throughout Colorado Springs reek of marijuana, as producers fill rental homes with plants.

Five years of retail pot coincide with five years of a homelessness growth rate that ranks among the highest rates in the country. Directors of homeless shelters, and people who live on the streets, tell us homeless substance abusers migrate here for easy access to pot.

Five years of Big Marijuana ushered in a doubling in the number of drivers involved in fatal crashes who tested positive for marijuana, based on research by the pro-legalization Denver Post.

Five years of commercial pot have been five years of more marijuana in schools than teachers and administrators ever feared.

“An investigation by Education News Colorado, Solutions and the I-News Network shows drug violations reported by Colorado’s K-12 schools have increased 45 percent in the past four years, even as the combined number of all other violations has fallen,” explains an expose on escalating pot use in schools by Rocky Mountain PBS in late 2016.

The investigation found an increase in high school drug violations of 71 percent since legalization. School suspensions for drugs increased 45 percent.

The National Survey on Drug Use and Health found Colorado ranks first in the country for marijuana use among teens, scoring well above the national average.

The only good news to celebrate on this anniversary is the dawn of another organization to push back against Big Marijuana’s threat to kids, teens and young adults.

The Marijuana Accountability Coalition formed Nov. 6 in Denver and will establish satellites throughout the state. It resulted from discussions among recovery professionals, parents, physicians and others concerned with the long-term effects of a commercial industry profiteering off of substance abuse.

“It’s one thing to decriminalize marijuana, it’s an entirely different thing to legalize an industry that has commercialized a drug that is devastating our kids and devastating whole communities,” said coalition founder Justin Luke Riley. “Coloradans need to know, other states need to know, that Colorado is suffering from massive normalization and commercialization of this drug which has resulted in Colorado being the number one state for youth drug use in the country. Kids are being expelled at higher rates, and more road deaths tied to pot have resulted since legalization.”

Commercial pot’s five-year anniversary is an odious occasion for those who want safer streets, healthier kids and less suffering associated with substance abuse. Experts say the worst effects of widespread pot use will culminate over decades. If so, we can only imagine the somber nature of Big Marijuana’s 25th birthday.

Source: Five Years Later, Colorado Sees Toll of Pot Legalization (illinoisfamily.org) February 2017

(Reuters Health) – Cannabis use by mothers or fathers during pregnancy, or even only before pregnancy, is associated with an increased risk of psychotic-like episodes in their children, a Dutch study suggests.

Because pot use by mothers and fathers carried similar risk, and a mother’s use before pregnancy had the same effect as use during pregnancy, the study team speculates that parental pot use is likely a marker for genetic and environmental vulnerability to psychotic experiences rather than a cause, and could be useful for screening kids at risk for psychosis later in life.

Babies exposed to cannabis in the womb do have an increased risk of being underweight and unusually small when they’re born and developing cognitive and behavior problems early in life, the researchers note in Schizophrenia Research. Cannabis can also cause hallucinations in adults, particularly with frequent use and at high doses, but less is known about the potential for infants exposed to the drug in the womb to develop psychotic-like symptoms.

For the study, researchers examined data from questionnaires asking 3,692 10-year-olds whether they had symptoms that are similar to what adults might experience with psychosis: hearing voices that nobody else detects, seeing things others don’t see, and having thoughts that others might find strange.

They also examined mothers’ reports on their own marijuana use as well as any use by their partners, and they also looked at lab tests for signs of cannabis in mothers’ urine.

When mothers used marijuana during pregnancy, children were 38 percent more likely to have these psychotic-like symptoms than the children of mothers who abstained from use during pregnancy, the study found. But children of mothers who used pot only before, but not during, pregnancy also had a 39 percent higher risk than the kids of mothers who didn’t use it.

Fathers’ cannabis use during pregnancy, meanwhile, was associated with a 44 percent greater likelihood of psychotic-like experiences in their kids.

“Some children with psychotic experiences are at increased risk to develop psychosis or other psychiatric disorders,” said lead study author Dr. Koen Bolhuis, a researcher at Erasmus Medical Center Rotterdam in the Netherlands.

“Unfortunately very little is known about how to treat psychotic experiences in children, or to prevent them from getting worse,” Bolhuis said by email.

Psychotic-like experiences aren’t disabling or frequent enough to be classified as psychosis, a severe mental health disorder in which patients’ thoughts and emotions are impaired on such a regular basis that they routinely experience delusions and hallucinations that make it impossible to know what’s real and what isn’t.

Psychosis can be caused by schizophrenia, and it can also happen as a result of some other medical conditions and as a side effect of certain prescription medications or illegal drugs.

In the current study, mothers who used cannabis during pregnancy were more likely than other women to smoke and drink during pregnancy, which can both independently influence the risk of emotional and behavioral health problems in children. They were also more likely to have partners who used cannabis while they were pregnant.

The study wasn’t a controlled experiment designed to prove whether or how cannabis exposure might directly cause psychotic experiences in children.

Researchers also lacked data on how much of infants’ cannabis exposure came from parent’s smoking versus ingesting pot.

With inhaled cannabis, it’s difficult to separate the impact of the drug itself from the effect of carbon monoxide also released in the smoke, noted Marcel Bonn-Miller of the University of Pennsylvania Perelman School of Medicine in Philadelphia.

“Carbon monoxide is a known toxicant which causes hypoxia, or oxygen deprivation, which has several well-known and well-studied detrimental effects on pregnancy and offspring development,” Bonn-Miller, who wasn’t involved the study, said by email.

Still, the current study results add to evidence that there’s no safe amount of cannabis exposure for babies in the womb, said Dr. Nathaniel DeNicola of George Washington University in Washington, D.C.

“We have sufficient data and biologic plausibility that marijuana use during pregnancy increases the risk of preterm birth and growth restricted babies,” DeNicola, who wasn’t involved the study, said by email. “The data is mixed on stillbirth, but still cause for concern.”

Source: Pot smoking by parents tied to risk of psychotic episodes in kids | Reuters August 2018

Last June, under huge and hysterical media pressure, Home Secretary Sajid Javid opened the lid on the Pandora’s box of ‘medicinal’ cannabis. He issued emergency licences to allow access for two young boys with severe forms of epilepsy and at the same time ordered a review into evidence of its therapeutic efficacy, falling for what soon transpired to be a well-orchestrated campaign. Coordinated by Volteface, the openly pro-legalising recreational cannabis think tank funded by Paul Birch, a multi-millionaire British tech tycoon, it was aided by the journalist and campaigner Ian Birrell, who has disclosed his membership of its advisory panel. Mrs Caldwell and her sick child had, the Daily Mail argued, been hijacked by a pro-cannabis lobby that stands to make billions. She herself has a vested interest as the director of a company marketing cannabis oil which she sells online.

With useful idiots like Lord Hague ready to make two and two add up to five by arguing that the current law is indefensible and therefore we must legalise cannabis altogether, the campaign had got off to a flying start.

Since then the media onslaught of the metro-elite’s demands for legal access to this drug has not stopped. Fuelled by Canada’s ill-considered decision to legalise recreational use, it reached peak volume last week. Kate Andrews of the Institute of Economic Affairs made her case for it based on a startlingly under-informed account of post-legal pot Colorado (she cannot have read the latest impact update) and arrest stats from the American Civil Liberties Union. Whatever their reliability, she should know that here you are unlikely to receive a custodial sentences before at least seven previous convictions or cautions, and that 50 per cent sent to prison for the first time have at least 15 ‘previous’. As to cannabis possession, it is a myth that is anything other than decriminalised already.

Then we had former Met Chief Lord Hogan-Howe adding his pennyworth. He has no reason not to know the devasting evidence from Colorado and Washington State, yet he thinks we need a two-year review of legalisation. Philip Collins of the Times seems equally gung-ho about Colorado’s descent into a dangerous drugs products free-for-all.

In the most sickeningly selfish article of all, the gloating Simon Jenkins raised his ‘glass of cannabis wine’ to the drug culture that no legalisation will ever sanitise.

Unmentioned was that Canada’s decision was based on no evidence at all that it would either reduce youth use or meaningfully curtail the black market, the stated goals for taking the country down this path

Nor was the fact that Canada’s ‘journey’ had started – where else? – with medicinal cannabis, the cannabis lobby’s admitted and cynical strategy to buy the drug a good name and lower the public’s defences.

This is the wheeze our Home Secretary has fallen for. He has already made good his promise of June 26 and given the all-clear for clinical specialists routinely to prescribe cannabis oil and similar products for epilepsy and multiple sclerosis. Taking effect on November 1, this decision is based on the hastily prepared recommendation of his Chief Medical Officer, Dame Sally Davies, that vaguely designated ‘cannabis based medicinal products’ should be ‘rescheduled’ (in other words, legalised for ‘prescription’).

This comes before the Advisory Council on the Misuse of Drugs (ACMD) recommendations have been followed through for a clear definition of what a cannabis-derived medicinal product is, and ‘additional frameworks’ and clinical guidance for ‘checks and balances’ for safe prescribing.

Yet these are products neither clinically tested nor of proven efficacy, which doctors will be under great pressure to prescribe and which will leak into the illegal market.

In this one misguided action, oblivious to those interests ruthlessly exploiting the medicinal cannabis pipe dream, the Home Secretary has casually trashed the UK’s world class and purposefully onerous pharmaceutical approval system.

The Home Secretary cannot have read the small print of Dame Sally’s review, or he chose not to, in his rush to get the Billy Caldwell story off the front pages. It has the hallmarks of a dodgy dossier. For the American evidence on which it relies states that there is ‘no or insufficient evidence to support or refute the conclusion that cannabis or cannabinoids are an effective treatment for epilepsy’.* Likewise the meta-analysis Dame Sally leant on provided her with no evidence for epilepsy.

The only ‘conclusive or substantial’ the American evidence finds is for the treatment of chronic pain in adults, chemotherapy-induced nausea and vomiting and for improving patient-reported multiple sclerosis spasticity symptoms. For these conditions the licensed cannabis-based drugs Sativex, Marinol and Nabilone exist.

Elsewhere the serious problems associated with the medicalisation of cannabis have been set out. The testimonial evidence it largely relies on falls short of the standards required for the approval of other drugs – which are ‘adequately powered, double blind, placebo controlled randomised clinical trials’.

Against this absence of evidence is the very real evidence of the drug’s harm which has presented itself again in rising hospital cannabis admissions. These include alarmingly high numbers of teens urgently admitted with psychosis. Had Dame Sally had taken more time, extended her search and listened to recent warnings, she would have found that this is far from the only public health risk associated with cannabis.

A long, well-written and referenced article in the BMJ by an Australian academic, Professor Albert Reece, entitled Known Cannabis Teratogenicity Needs to be Carefully Considered, published shortly after the Davies review, raises the alarming question of whether exposure to cannabis has significance for rising birth defects; and whether full-spectrum cannabis (unlike the FDA-approved drug Epidiolex) could have some of the problems of thalidomide.

Reece’s concern is that even were the clinical efficacy of cannabinoids to be demonstrated, ‘their teratogenic potential, from both mother and father’ would need to be carefully balanced with their clinical utility. A teratogen, for the uninitiated, is an agent that can disrupt the development of the embryo or foetus and halt the pregnancy or produce a congenital malformation (a birth defect).

Professor Reece reports that ‘gestational cannabis has been linked with a clear continuum of birth defects’ in a range of longitudinal studies, and increased foetal death, and reflects a worldwide increase in high cannabis-using areas.

He is not alone to be concerned. The website of NHS Wales carries a warning about cannabis which indicates that it is taking its gastroschisis (a condition in which the bowel herniates out of the abdomen during foetal development) outbreak seriously.

The question of whether cannabis is to blame for rising rates of gastroschisis has been raised elsewhere and those puzzled by it cite drug use as a risk factor, as does the NHS. 

Professor Reece’s warning needs heeding. Only once before has a known teratogen been marketed globally: thalidomide. What the Home Secretary and his Chief Medical Officer need reminding of, as Reece makes clear, is that the thalidomide disaster is ‘the proximate reason for modern pharmaceutical laws’. These are laws that Sajid Javid, Dame Sally Davies and the AMCD are prematurely prepared to overturn.

Previously supportive commentators have begun to express their reservations about the implications of ‘medicinal’ cannabis. It can’t be allowed to become a free-for-all, writes Alice Thomson in the Times.

She is right to worry, and the dangers could be worse than anything she has imagined.

This is why the Home Secretary needs to stop and take stock. He still has time to review and revoke his ill-advised and media-pressured decision. As for the vested interests behind legalising cannabis, he should know that as far as medicinal cannabis is concerned more will never be enough.

*Epidiolex, the GW Pharmaceuticals CBD-based epilepsy drug which has recently been approved for Dravet Syndrome in the US and which we can expect to be approved in Europe, does not fall into this category. One must presume that GW Pharma with twenty years of research would have included the psychoactive ingredient that Mrs Caldwell and her campaign claim is necessary, had they been able to justify it clinically.

Source: The Home Secretary has acted prematurely and dangerously on medical cannabis – The Conservative Woman October 2018

Source: What about the children? | DB Recovery Resources October 2018

DRIVING WHILE HIGH is a growing problem in the U.S. Estimates show that a third of impaired driving incidents can be traced to marijuana, while many more involve a combination of multiple substances.

In Colorado, marijuana-related traffic deaths increased by 48 percent after the state legalized recreational use of the drug. In Washington State, 18.6% of all DUI cases in the state tested for drugs were positive for THC; from January through April, 2015, 33% were positive for THC. The number of fatally injured drivers positive for marijuana in the state more than doubled following marijuana legalization, reaching 17% in 2014.

Even as Colorado’s population has increased, fatal crashes in CO related to alcohol-impaired drivers have fallen during the era of recreational pot legalization, from 160 in 2011 to 143 in 2015 (crashes where Blood Alcohol Content, BAC, was greater than or equal to 0.08 percent), an 11 percent drop over four years. At the same time, traffic fatalities overall have risen, from 447 in 2011 to 608 in 2016, a 26 percent rise over five years, as drivers testing positive for marijuana use have risen sharply.

AAA has released guidelines on impaired driving that are important to remember. First, there is no science showing that drivers reliably become impaired after ingesting a specific amount of marijuana. This is very different from alcohol, and we could never count on a 0.08 BAC level equivalent for marijuana. Second, research has not been able to reliably measure impairment based on THC levels. THC blood levels fall so rapidly that such measured levels are vastly lower than when the impaired driving occurred due to the long delay in testing. But the effect on driving persists beyond the feeling of being high.

One groundbreaking study found that that chronic
marijuana use can impair a person’s ability to drive for up to three weeks after stopping marijuana use.

Other research has noted non-chronic users who
smoke one or two marijuana joints are likely to test
positive for marijuana at standard cut – off levels for only 2 – 3 days, with many testing negative 24
hours after smoking marijuana. After three to five
days, such users almost always test negative.

Furthermore, marijuana-impaired driving is likely an underreported problem, since many drivers high on marijuana are also using alcohol. Since there is an established standard for drunk driving, the criminal justice system often stops at a lab test showing greater than 0.08 BAC levels.

DRIVING WHILE HIGH is an unappreciated problem, compounded by a growing industry intent on protecting their brand and image. A recent Liberty Mutual survey found that a third of students said driving under the influence of marijuana is legal in states where it is recreational. More than 20% of teens reported it’s common among their friends. Parent perceptions were similar: 27% said it’s legal and 14% said it’s common among friends. A phttps://learnaboutsam.org/ublic education campaign on the dangers of driving while high is vital.

Source: Leaflet from SAM (Smart Approaches to Marijuana)

Health experts blame lack of messaging about responsible use of powerful cannabis products

Your life can change in an instant:
Fast facts about drug-impaired driving (DID)

• 50% of cannabis users don’t think that drugs affect their driving much, while 1 in 5 don’t think it has any negative effect at all.
• Over 1 in 3 – 39% of those who have used cannabis in the past year have driven within two hours of consuming cannabis.
• 149 – Number of fatally injured Canadian drivers who tested positive for cannabis in 2014.
• 3,098 – Number of DID incidents reported in Canada in 2016.
• 2 in 5 – Approximate number of people who were a passenger in a vehicle driven by someone who had recently used cannabis.
• Drugs impair your: balance and coordination, motor skills, judgement, reaction time, attention, decision-making skills 
• Every 3 hours – How often a drug-impaired driving offence is recorded in Canada
• Increases likelihood – Recent research shows a 1.3- to 3.0-fold increase in risk of a motor vehicle collisions after cannabis use.
• 1000$ + a 1-year suspension – Minimum penalty if you are caught driving impaired

#dontdrivehigh

Use public transit
Use a designated
Call someone for a ride
Cab or ride-share
Stay over

Source: Don’t Drive High. Your life can change in an instant: Fast facts about drug-impaired driving (DID) – Canada.ca December 2019

(Denver, CO) – A new state-funded report out of Colorado found that the state continues to hold the top ranking when it comes to past month use of marijuana, more young children are being exposed to highly potent pot products, use of edibles and vaping/dabbing is way up among high school students, and emergency department visits have increased. 

“The data in this report show that Colorado’s marijuana industry is threatening public health,” said Luke Niforatos Senior Policy Advisor to Smart Approaches to Marijuana (SAM) and longtime Colorado resident. “Just last year, the industry was caught recommending pot to pregnant mothers. It’s time to start holding them accountable.”

According to the report, past month use has increased 14% over the last year and adult use in the state of Colorado continues to be significantly higher than the national average. Young adults, aged 18-25 reported the greatest instance of past month use at 29.2%. This is concerning as this age group is still in a crucial period of brain development and heavy use at this age can lead to the development of serious mental health issues. 

Adult Past Month Marijuana Use 

The report notes that “at least 23,009 homes with children in Colorado may not be storing marijuana products safely, which increases the risk of accidental ingestion.” On this front, the report also finds that calls to the poison center for marijuana exposure to young children remains high after it began skyrocketing following legalization. Prior to legalization, there was an average of 5 calls per year related to marijuana exposure in children under the age of nine. After legalization, this number shot up to 27 in 2013, 45 in 2014, 40 in 2016, and now 50 in 2017. Ingestion of marijuana edibles comprised 65% of these reports. Additionally, the report finds that approximately 32,800 homes with children 1-14 years old had possible secondhand marijuana smoke or vapor exposures.

Number of Children Exposed to Marijuana

Of note, this report still fails to accurately depict the real data when it comes to youth use in Colorado. The findings on rates of youth use are based on data collected by the Healthy Kids Colorado Survey which suffers from multiple methodological issues. That fact notwithstanding, according to the flawed HKCS data, past month edible use is up significantly among high school students, rising 22% since 2015. Additionally, the “dabbing” of high potency THC concentrates has increased 43% since 2015 among high schoolers.

“As a Colorado physician, I am incredibly concerned with the findings of this report,” said Dr. Ken Finn, a pain doctor in Colorado Springs. “The harms to public health that are documented here are alarming, especially the rising risk of exposure of pot products to young children whose brains are still in development. Additionally, I find this report to be sorely lacking key data points, such as the fact that marijuana is the most prevalent substance found in Colorado completed teen suicide. The state needs to get serious with the documentation of the real consequences of marijuana legalization.”

“Is this the type of outcome people wanted when they voted to legalize? Tens of thousands of young people in Colorado are now living in homes where they are either actively breathing in marijuana smoke or are at risk of eating highly potent THC gummies, candies, brownies, and ice creams,” said Niforatos. “As public health and safety professionals, we will continue to hold the state accountable for this reckless policy of marijuana commercialization.”

Source:  learnaboutSam.org  Feb.2019

Free-marketeers are ignoring the devastating harm it can do as they champion consumer rights.

Four men had to be rescued last weekend from England’s highest mountain, Scafell Pike, after becoming “incapable of walking due to cannabis use”. Said Cumbria police: “Words fail us.”

Well, yes. Does everyone agree that these men placed an irresponsible burden on a public service? Apparently so. Does everyone agree that the use of cannabis should be discouraged to reduce its irresponsible burden on society? Well, no; quite the opposite.

Last week Prince William raised the “massive issue” of drug legalisation. Although he expressed no opinion, merely to raise it was inescapably to express one, since the only people for whom it is a “massive issue” are those who promote it.

At the Labour Party conference yesterday the comedian Russell Brand called for drugs to be decriminalised. At next week’s Conservative conference, the free-market Adam Smith Institute will be pushing for the legalisation of cannabis. Legalisation means more users. That means more harm, not just to individuals but to society. The institute, however, describes cannabis as “a low-harm consumer product that most users enjoy without major problems”. What? A huge amount of evidence shows that far from cannabis being less harmful than other illicit drugs, as befits its Class B classification, its effects are far more devastating. Long-term potheads display on average an eight-point decline in IQ over time, an elevated risk of psychosis and permanent brain damage.

Cannabis is associated with a host of biological ill-effects including cirrhosis of the liver, strokes and heart attacks. People who use it are more likely than non-users to access other illegal drugs. And so on.

Ah, say the autonomy-loving free-marketeers, but it doesn’t harm anyone other than the user. Well, that’s not true either. It can destroy relationships with family, friends and employers. Users often display more antisocial behaviour, such as stealing money or lying to get a job, as well as a greater association with aggression, paranoia and violent death. According to Stuart Reece, an Australian professor of medicine, cannabis use in pregnancy has also been linked to an epidemic of gastroschisis, in which babies are born with intestines outside their abdomen, in at least 15 nations including the UK.

Long-term potheads display on average an eight-point drop in IQ

The legalisers’ argument is that keeping cannabis illegal does not control the harm it does. Yet wherever its supply has been liberalised, its use and therefore the harm it does have both gone up. In 2001 Portugal decriminalised illegal drugs including cocaine, heroin and cannabis. Sparked by a report by the American free-market Cato Institute, which claimed this policy was a “resounding success”, Portugal has been cited by legalisers everywhere as proof that liberalising drug laws is the magic bullet to erase the harm done by illegal drugs.

The truth is very different. In 2010 Manuel Pinto Coelho, of the Association for a Drug Free Portugal, wrote in the BMJ: “Drug decriminalisation in Portugal is a failure . . . There is a complete and absurd campaign of manipulation of facts and figures of Portuguese drug policy . . .”

According to the Portuguese Institute for Drugs and Drug Addiction, between 2001 and 2007 drug use increased by 4.2 per cent, while the number of people who had used drugs at least once rose from 7.8 per cent to 12 per cent. Cannabis use went up from 12.4 per cent to 17 per cent.

The latest evidence about Portugal, a study by the Intervention Service for Addictive Behaviours and Dependencies, shows “a rise in the prevalence of every illicit psychoactive substance from 8.3 per cent in 2012 to 10.2 per cent in 2016-17”, with most of that rise down to increased cannabis use.

For free-marketeers, this evidence of devastating harm to individuals and society is irrelevant. Nothing can be allowed to dent their dogmatic belief that all human life is a transaction, market forces are a religion and the rights of the consumer are sacrosanct. Says the Adam Smith Institute about cannabis legalisation: “The object isn’t harm elimination, it’s not even harm reduction alone, it’s utility maximisation.” In other words, they want as many people as possible to be puffing on those spliffs.

Free-market libertarians are nothing if not consistent. They oppose policies to reduce social harm across the board. Smoking curbs, mandatory seat-belts, speed cameras, gambling restrictions, controls to end unmanageable immigration — they’ve been against them all.

Despite how they are viewed, there’s nothing conservative about the free-marketeers. Far from conserving legal or social constraints, they want to tear them down in the name of consumer choice. The classical political thinkers they quote in support of applying market principles to every aspect of society never in fact subscribed to such a doctrine. Far from putting the autonomous self on a pedestal, Adam Smith himself in his Theory of Moral Sentiments put personal rights last and the interests of others first.

The distortion of such thinking is why Russell Brand and the Adam Smith Institute are soul mates. In a fearful symmetry, both the left and the free-market right deny the importance of conserving the social good. One calls it paternalism, the other the nanny state. Both are radically irresponsible and destructive. The only difference is the gender. And even that, in our current lifestyle free-for-all, is now surely up for grabs.

Source: Thinking is warped on cannabis legalisation (thetimes.co.uk) September 2017

This Notice of Liability Memo and attached Affidavit of Harms give formal notification to all addressees that they are morally, if not legally liable in cases of harm caused by making toxic marijuana products legally available, or knowingly withholding accurate information about the multiple risks of hemp/marijuana products to the Canadian consumer.  This memo further gives notice that those elected or appointed as representatives of the people of Canada, by voting affirmatively for Bill C45, do so with the knowledge that they are breaching international treaties, conventions and law.  They do so also with the knowledge that Canadian law enforcement have declared that they are not ready for implementation of marijuana legalization, and as they will not be ready to protect the lives of Canadians, there may arise grounds for a Charter of Rights challenge as all Canadian citizens are afforded a the right to security of self.

Scientific researchers and health organizations raise serious questions about the safety of ingesting even small amounts of cannabinoids. Adverse effects include risk of harm to the cardio-vascular system, respiratory tract, immune system, reproductive and endocrine systems, gastrointestinal system and the liver, hyperemesis, cognition, psychomotor performance, psychiatric effects including depression, anxiety and bipolar disorder, schizophrenia and psychosis, a-motivational syndrome, and addiction.  The scientific literature also warns of teratogenicity (causing birth deformities) and epigenetic damage (affecting genetic development) and clearly establishes the need for further study. The attached affidavit cites statements made by Health Canada that are grounded in scientific evidence that documents many harms caused by smoking or ingesting marijuana.  

Putting innocent citizens in “harm’s way” has been a costly bureaucratic mistake as evidenced by the 2015 Canadian $168 million payout to victims of exposure to the drug thalidomide. Health Canada approved thalidomide in 1961 to treat morning sickness in pregnant women but it caused catastrophic birth defects and death.

It would be instructive to reflect on “big tobacco” and their multi-billion-dollar liability in cases of misinformed sick and dead tobacco cigarette smokers. Litigants won lawsuits for harm done by smoking cigarettes even when it was the user’s own choice to obtain and smoke tobacco. In Minnesota during the 1930’s and up to the 1970’s tobacco cigarettes were given to generally healthy “juvenile delinquents’ incarcerated in a facility run by the state.  One of the juveniles, now an adult, who received the state’s tobacco cigarettes, sued the state for addicting him. He won.

The marijuana industry, in making public, unsubstantiated claims of marijuana safety, is placing itself in the same position, in terms of liability, as the tobacco companies.
In 1954, the tobacco industry published a statement that came to be known during Minnesota’s tobacco trial as the “Frank Statement.” Tobacco companies then formed an industry group for the purposes of deceiving and confusing the public.

In the Frank Statement, tobacco industry spokesmen asserted that experiments linking smoking with lung cancer were “inconclusive,” and that there was no proof that cigarette smoking was one of the causes of lung cancer. They stated, “We believe the products we make are not injurious to health.” Judge Kenneth Fitzpatrick instructed the Minnesota jurors: “Jurors should assume in their deliberations that tobacco companies assumed a “special duty” by publishing the ad (Frank Statement), and that jurors will have to determine whether the industry fulfilled that duty.” The verdict ruled against the tobacco industry.

Effective June 19, 2009, marijuana smoke was added to the California Prop 65 list of chemicals known to cause cancer. The Carcinogen Identification Committee (CIC) of the Office of Environmental Health Hazard Assessment (OEHHA) “determined that marijuana smoke was clearly shown, through scientifically valid testing according to generally accepted principles, to cause cancer.”

Products liability and its application to marijuana businesses is a topic that was not discussed in the Senate committee hearings. Proposition 65, requires the State to publish a list of chemicals known to cause cancer, birth defects or other types of reproductive harm. Proposition 65 requires businesses to provide their customers with notice of these cancerous causing chemicals when present in consumer products and provides for both a public and private right of action.

The similarities between the tactics of “Big Tobacco” and the “Canadian Cannabis Trade Alliance Institute” and individual marijuana producers would seem to demand very close scrutiny. On May 23, a witness testified before the Canadian Senate claimed that marijuana is not carcinogenic. This evidence was not challenged.

The International Narcotics Control Board Report for 2017 reads: “Bill C-45, introduced by the Minister of Justice and Attorney General of Canada on 13 April 2017, would permit the non-medical use of cannabis. If the bill is enacted, adults aged 18 years or older will legally be allowed to possess up to 30 grams of dried cannabis or an equivalent amount in non-dried form. It will also become legal to grow a maximum of four cannabis plants, simultaneously for personal use, buy cannabis from licensed retailers, and produce edible cannabis products. The Board wishes to reiterate that article 4 (c) of the 1961 Convention restricts the use of controlled narcotic drugs to medical and scientific purposes and that legislative measures providing for non-medical use are in contravention of that Convention….

The situation pertaining to cannabis cultivation and trafficking in North America continues to be in flux owing to the widening scope of personal non-medical use schemes in force in certain constituent states of the United States. The decriminalization of cannabis has apparently led organized criminal groups to focus on manufacturing and trafficking other illegal drugs, such as heroin. This could explain why, for example, Canada saw a 32 per cent increase from 2015 to 2016 in criminal incidents involving heroin possession….The Canadian Research Initiative in Substance Misuse issued “Lower-risk cannabis use guidelines” in 2017. The document is a health education and prevention tool that acknowledges that cannabis use carries both immediate and long-term health risks.”

https://www.incb.org/documents/Publications/AnnualReports/AR2017/Annual_Report_chapters/Chapter_3_Americas_2017.pdf

Upon receipt of this Memo and Affidavit, the addressees can no longer say they are ignorant or unaware that promoting and/or distributing marijuana cigarettes for recreational purposes is an endangerment to citizens. Receipt of this Memo and Affidavit removes from the addressees any claim of ignorance as a defense in potential, future litigation.

Pamela McColl www.cleartheairnow.org

pam.mccoll@cleartheairnow.org

AFFIDAVIT May 27, 2018

I, Pamela McColl, wish to inform agencies and individuals of known and potential harm done/caused by the use of marijuana (especially marijuana cigarettes) and of the acknowledgement the risk of harm by Health Canada. 

Marijuana is a complex, unstable mixture of over four hundred chemicals that, when smoked, produces over two thousand chemicals.  Among those two thousand chemicals are many pollutants and cancer-causing substances.  Some cannabinoids are psychoactive, all are bioactive, and all may remain in the body’s fatty tissues for long periods of times with unknown consequences. Marijuana smoke contains carcinogenic (cancer-causing) substances such as benzo(a)pyrene, benz(a)anthracene, and benzene in higher concentrations than are present in tobacco smoke.  The mechanism by which benzo(a)pyrene causes cancer in smokers was demonstrated scientifically by Denissenko MF et al. Science 274:430-432, 1996. 

Health Canada Consumer Information on Cannabis reads as follows:  “The courts in Canada have ruled that the federal government must provide reasonable access to a legal source of marijuana for medical purposes.”

“Cannabis is not an approved therapeutic product and the provision of this information should not be interpreted as an endorsement of the use of cannabis for therapeutic purposes, or of marijuana generally, by Health Canada.”

“Serious Warnings and Precautions: Cannabis (marihuana, marijuana) contains hundreds of substances, some of which can affect the proper functioning of the brain and central nervous system.”

“The use of this product involves risks to health, some of which may not be known or fully understood. Studies supporting the safety and efficacy of cannabis for therapeutic purposes are limited and do not meet the standard required by the Food and Drug Regulations for marketed drugs in Canada.”

Health Canada – “When the product should not be used: Cannabis should not be used if you:-are under the age of 25 -are allergic to any cannabinoid or to smoke-have serious liver, kidney, heart or lung disease -have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder-are pregnant, are planning to get pregnant, or are breast-feeding -are a man who wishes to start a family-have a history of alcohol or drug abuse or substance dependence Talk to your health care practitioner if you have any of these conditions. There may be other conditions where this product should not be used, but which are unknown due to limited scientific information.

Cannabis is not an approved therapeutic product and the provision of this information should not be interpreted as an endorsement of the use of this product, or cannabis generally, by Health Canada.”

Prepared by Health Canada Date of latest version: February 2013, accessed May 2018. https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-use-marijuana/information-medical-practitioners/information-health-care-professionals-cannabis-marihuana-marijuana-cannabinoids.html

A report published by survey company RIWI Corp. (RIWI.com) can be found at: https://riwi.com/case-study/measuringcanadians-awareness-of-marijuanas-health-effects-may-2018

The report measures Canadians’ awareness of marijuana’s health effects as determined by Health Canada and published on Health Canada’s website. RIWI data indicates: 1. More than 40% of those under age 25 are unaware that marijuana impacts safe driving. Further, 21% of respondents are not aware that marijuana can negatively impact one’s ability to drive safely. Health Canada: “Using cannabis can impair your concentration, your ability to make decisions, and your reaction time and coordination. This can affect your motor skills, including your ability to drive.” 2. One in five women aged 25-34 believes marijuana is safe during pregnancy, while trying to get pregnant, or breastfeeding. • RIWI: “For women of prime childbearing age (25-34), roughly one in five believe smoking marijuana is safe during pregnancy, planning to get pregnant, and breastfeeding.” • Health Canada: “Marijuana should not be used if you are pregnant, are planning to get pregnant, or are breastfeeding. … Long-term use may negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy.” 3. One in three Canadians do not think that marijuana is addictive. • Health Canada: “Long term use may result in psychological dependence (addiction).” 4. One in three Canadians believe marijuana aids mental health. • Health Canada: “Long term use may increase the risk of triggering or aggravating psychiatric and/or mood disorders (schizophrenia, psychosis, anxiety, depression, bipolar disorder).” 5. One in two males were unaware that marijuana could harm a man’s fertility • “Marijuana should not be used if you are a man who wishes to start a family.”

ClearTheAirNow.org, a coalition of concerned Canadians commissioned the survey.

Affiant is willing to provide further sources of information about the toxicity of marijuana.

Pamela McColl

www.cleartheairnow.org

pam.mccoll@cleartheairnow.org

Source: From email sent to Drug Watch International May 2018

Abstract

Source: Effects of marijuana on reproductive health: preconception a… : Current Opinion in Endocrinology, Diabetes and Obesity (lww.com) December 2021

Click here to view the video

Source: Chronic State from DrugFree Idaho, Inc. on Vimeo. July 2018

Abstract

Source: Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity | Science May 2007

Reproductive and Cancer Hazard Assessment Branch Office of Environmental Health Hazard Assessment California Environmental Protection Agency

PREFACE

The Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65, California Health and Safety Code 25249.5 et seq.) requires that the Governor cause to be published a list of those chemicals “known to the state” to cause cancer or reproductive toxicity. The Act specifies that “a chemical is known to the state to cause cancer or reproductive toxicity … if in the opinion of the state’s qualified experts the chemical has been clearly shown through scientifically valid testing according to generally accepted principles to cause cancer or reproductive toxicity.”

The lead agency for implementing Proposition 65 is the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency. The “state’s qualified experts” regarding findings of carcinogenicity are identified as the members of the Carcinogen Identification Committee (CIC) of the OEHHA Science Advisory Board (Title 27 Cal. Code of Regs. §25301; formerly Title 22, Cal. Code of Regs. §12301). OEHHA announced the selection of marijuana smoke as a chemical for consideration for listing by the CIC in the California Regulatory Notice Register on December 12, 2007, subsequent to consultation with the Committee at their November 19, 2007 meeting.

 At that meeting, the Committee advised OEHHA to prepare hazard identification materials for marijuana smoke. The December 12th notice also marked the start of a 60-day public request for information relevant to the assessment of the evidence on the carcinogenicity marijuana smoke. No information was received as a result of this request. This document was released as a draft document in March 2009 for a 60-day public comment period. No public comments were received.

The draft document provided the Committee with the available scientific evidence on the carcinogenic potential of this chemical. The current document is the final version of the document that was discussed by the Committee at their May 29, 2009 meeting. At their May 29, 2009 meeting the Committee, by a vote of five in favor and one against, found that marijuana smoke had been “clearly shown through scientifically valid testing according to generally accepted principles to cause cancer.” Accordingly, marijuana smoke was placed on the Proposition 65 list of chemicals known to the state to cause cancer.

 EXECUTIVE SUMMARY

 Marijuana smoke is formed when the dried flowers, leaves, stems, seeds and resins of plants in the genus Cannabis are burned. Marijuana smoke aerosol contains thousands of organic and inorganic chemicals, including psychoactive cannabinoids, which are unique to Cannabis plants. Inhaling marijuana smoke for its psychotropic properties became popular in western cultures in the 1960s, though marijuana has been used for medicinal and psychotropic purposes in other parts of the world for thousands of years. In California, use of marijuana for physician recommended purposes has been legal under state law since 1996 when Proposition 215, the Compassionate Use Act, was passed by state voters. However, the vast majority of marijuana use continues to be for recreational purposes, which remains illegal.

Marijuana smoke and tobacco smoke share many characteristics with regard to chemical composition and toxicological properties. At least 33 individual constituents present in both marijuana smoke and tobacco smoke are already listed as carcinogens under Proposition 65. In examining the potential carcinogenicity of marijuana smoke, a range of information was evaluated. Studies of cancer risk in humans and laboratory animals exposed to marijuana smoke were reviewed. Other relevant data, including studies investigating genotoxicity and effects on endocrine function, cell signalling pathways, and immune function caused by marijuana smoke, were all considered. Also of interest were the similarities in chemical composition and in toxicological properties between marijuana smoke and tobacco smoke, and the presence of numerous carcinogens in marijuana smoke. The findings of all these reviews are summarized below.

There is evidence from some epidemiological studies of people exposed to marijuana smoke suggestive of increased cancer risk from both direct and parental marijuana smoking. However, this evidence is limited by potential biases and small numbers of studies for most types of cancer. Studies reporting results for direct marijuana smoking have observed statistically significant associations with cancers of the lung, head and neck, bladder, brain, and testis. The strongest evidence of a causal association was for head and neck cancer, with two of four studies reporting statistically significant associations. The evidence was less strong but suggestive for lung cancer, with one of three studies conducted in populations that did not mix marijuana and tobacco reporting a significant association. Suggestive evidence also was seen for bladder cancer, with one of two studies reporting a significant association. For brain and testicular cancers, the single studies conducted of each of these endpoints reported significant associations.

Among the epidemiological studies that reported results for parental marijuana smoking and childhood cancer, five of six found statistically significant associations. Maternal and paternal marijuana smoking were implicated, depending on the type of cancer. Childhood cancers that have been associated with maternal marijuana smoking are acute myeloid leukaemia, neuroblastoma, and rhabdomyosarcoma. Childhood cancers that have been associated with paternal marijuana smoking are leukaemia (all types), infant leukaemia (all types), acute lymphoblastic leukaemia, acute myeloid leukaemia, and rhabdomyosarcoma. A limitation common to the epidemiologic studies was potential bias from under-reporting of marijuana smoking due to its illegality, social stigma, lack of privacy during oral interviews, and subject desire to please interviewers, and possibly different degrees of under-reporting between cancer patients and healthy controls. Another limitation of several studies was that they were conducted in geographic locations where marijuana and tobacco are commonly mixed before smoking (e.g., three of six lung cancer studies and one of two bladder cancer studies were conducted in northern Africa, and two of four oral cancer studies were conducted in England). Thus, the results of those studies may have been confounded by the effects of exposure to tobacco smoke.

In animal studies, increases in squamous cell papilloma of the skin were reported in mice exposed dermally to marijuana smoke condensate. Malignant mesenchymatous tumors were reported following six subcutaneous injections of marijuana smoke condensate to newborn rats. In a marijuana smoke inhalation study in female rats, benign tumors of the ovary (serous cytoma and follicular cysts) and benign and malignant tumors of the uterus (adenofibroma, adenosarcoma, and telengiectatic cyst and polyps) were observed. Marijuana smoke condensate also exhibited tumor promoting activity in a mouse skin tumor initiation-promotion assay.

Evidence indicating that marijuana smoke is genotoxic includes findings that marijuana smoke induces mutations in Salmonella, and several small cytogenetic studies in humans suggesting that exposure to marijuana smoke may be associated with increased mutations and chromosomal abnormalities. While the data on the genotoxicity of marijuana smoke per se are limited, many individual smoke constituents have been shown to form DNA adducts, induce gene mutations, and damage chromosomes. Evidence indicating that marijuana smoke alters endocrine function includes findings for a number of different hormonal pathways. Marijuana smoke condensate has been shown to have estrogenic effects, including findings that it can activate the estrogen receptor (ER). Marijuana smoke also has been shown to have anti-estrogenic effects, through the induction of cytochrome P450 1A1 and the resultant increase in estrogen (E2) metabolism and through the inhibition of aromatase, an enzyme that converts testosterone to E2.

Other studies indicate that marijuana smoke condensate has anti-androgenic effects, inhibiting binding of dihydrotestosterone (DHT) to the androgen receptor (AR). Studies of ∆9 -tetrahydrocannabinol (∆9 -THC) and other cannabinoids provide evidence for disruption of the hypothalamic-pituitary-gonadal axis, including evidence that ∆9 -THC inhibits the release of follicle stimulating hormone, luteinizing hormone, prolactin, growth hormone, thyroid-stimulating hormone, and corticotrophin. These alterations in endocrine function can affect the growth of hormone responsive tissues,  and might increase the risk of certain cancers (e.g., testes, ovary, uterus, and breast).

 Evidence suggesting that marijuana smoke alters cell signalling pathways involved in cell cycle control comes from studies of the effects of ∆9 -THC and other cannabinoids on protein kinases. Depending upon the cell type and the dose administered, ∆9 -THC and other cannabinoids may either stimulate or inhibit cell proliferation. There is evidence that marijuana smoke suppresses the innate and adaptive immune response. The bactericidal activity of rat alveolar macrophages was reduced by marijuana smoke in vivo and in vitro. Tumoricidal and bactericidal activities were reduced in alveolar macrophages from marijuana smokers, compared to non-smokers. In addition, in one study smoking marijuana was associated with a more rapid progression of human immunodeficiency virus infection to acquired immunodeficiency syndrome. ∆9 -THC and other cannabinoids present in marijuana smoke have also been shown to suppress host resistance to microbial infection, macrophage function, natural killer and T cell cytolytic activity, cytokine production by macrophages and T cells, and to decrease antigen presentation by dendritic cells. These immunosuppressive effects could lead to an increased risk of cancer by reducing immunosurveillance capacity against neoplastic cells.

Prolonged exposures to marijuana smoke in animals and humans cause proliferative and inflammatory lesions in the lung, such as cellular disorganization, squamous metaplasia, and hyperplasia of basal and goblet cells (observed in the bronchial epithelial tissues of marijuana smokers). In summary, there is some evidence from studies in humans that marijuana smoke is associated with increased cancer risk. Studies in animals also provide some evidence that marijuana smoke induces tumors, with benign and malignant tumors observed in rats exposed via inhalation, malignant tumors in rats exposed via subcutaneous injection as newborns, and benign tumors in mice exposed dermally. Studies investigating the genotoxicity, immunotoxicity, and effects on endocrine function and cell signalling pathways provide additional evidence for the carcinogenicity of marijuana smoke. Finally, the similarities in chemical composition and in toxicological activity between marijuana smoke and tobacco smoke, and the presence of numerous carcinogens in marijuana (and tobacco) smoke, provide additional evidence of carcinogenicity.

Source: Evidence on the Carcinogenicity of Marijuana Smoke August 2009

The Internet hosts many unregulated marketplaces for otherwise regulated products. If extended to marijuana (or cannabis), online markets can undermine both the U.S. Controlled Substances Act, which bans marijuana sales, and the regulatory regimes of states that have legalized marijuana. Consequently, regardless of the regulatory regime, understanding the online marijuana market should be a public health
priority. Herein, the scale and growth trajectory of the online marijuana marketplace was assessed for the first time by analyzing aggregate Internet searches and the links searchers typically find.

METHODS
First, the fraction of U.S. Google searches including the terms marijuana, weed, pot, or cannabis relative to all searches was described monthly from January 2005 through June 2017 using data obtained from Google. Searches were also geotagged by state (omitting Alaska, Montana, North Dakota, South Dakota, Vermont, West Virginia, and Wyoming because of data access restrictions). The subset of shopping searches was then monitored by tracking queries that also included buy, shop, and order (e.g., buy marijuana) in aggregate. Searches that included killer, cooking, or clay (e.g., weed killer) were considered unrelated and excluded from all analyses.
Linear regressions were used to compute pooled means to compare between time periods and log-linear regressions were used to compute average growth. Raw search volumes were estimated based on total Google search volume using comScore (www.comscore.com).
Searches in a Google Chrome browser without cached data were executed during July 2017 using the 12 combinations of marijuana and shopping root terms (i.e., buy marijuana). The results would be indicative of a Google user’s typical search results. The first two pages of links, including duplicates (N¼279, with seven to 12 links per page), were analyzed (because nearly all searchers click a link on the first two pages, with as much as 42% selecting the first link). Investigators recorded whether each linked site advertised mail-order marijuana (excluding local deliveries in legal marijuana states) and its order in the search results. Two authors agreed on all labels. Analyses were computed using R, version 3.4.1.

RESULTS
Marijuana searches grew 98% (95% CI¼84%, 113%) as a proportion of all searches from 2005 through the partial 2017 year (Figure 1). The subset of marijuana searches indicative of shopping grew more rapidly over the same period (199%, 95% CI¼165%, 243%), with 1.4–2.4
million marijuana shopping searches during June 2017. Marijuana shopping searches were highest in Washington, Oregon, Colorado, and Nevada. The compounding annual growth rate for marijuana shopping searches since 2005 was significantly positive (po0.05) in 42 of
the 44 studied locations (all but Alabama and Mississippi), suggesting demand is growing across the nation. Forty-one percent (95% CI¼35%, 47%) of shopping search results linked to retailers promising mail-order marijuana (Table 1). Retailers occupied 50% (95% CI¼42%, 59%) of the first page results and for eight (of 12) searches, the first link led to a mail-order marijuana retailer. For some searches (e.g., order marijuana), all of the first-page links were marijuana retailers.

Table 1: Online Mail-Order Marijuana Retailers on Internet Search Engines, 2017

Note: Data were collected by executing searches in July 2017. Cells show the frequency and percent of links (by column) in the first two
pages of Google search results that claim to sell mail-order marijuana in response to 12 searches that contained unique combinations of the
following terms: cannabis, marijuana, pot, or weed with buy, order, or shop, such as buy cannabis, buy marijuana, buy pot, or buy weed.
Searches were executed on a new Google browser without cached data. Two authors agreed on the labels 100% of the time.

DISCUSSION
Millions of Americans search for marijuana online, and websites where marijuana can be purchased are often the top search result.
If only a fraction of the millions of searches and thousands of retailers are legitimate, this online marketplace poses a number of potential public health consequences. Children could purchase marijuana online. Marijuana could be sold in states that do not currently allow it.

Initiation and marijuana dependence could increase. Products may have inconsistent potency or be contaminated. State and local tax revenue (which can fund public health programs) could be negatively impacted.
Regulations governing online marijuana markets (even if policy changes favor legalized marijuana) need to be developed and enforced. Policing online regulations will require careful coordination across jurisdictions at the local, state, and federal level with agreements on how to implement regulations where enforcement regimes conflict. Online sales are already prohibited under virtually every regulatory regime—all sales are illegal under federal statute and legal marijuana states like Colorado ban online sales—yet the market appears to be thriving.
Government agencies might work with Internet providers to purge illicit marijuana retailers from search engines, similar to how Facebook removes drug-related pages. Moreover, online payment facilitators could refuse to support marijuana-related online transactions.
This study was limited in that who is buying/selling and the quantity of marijuana exchanged cannot be measured. Further, some searches may be unrelated to seeking marijuana retailers, and some retailers may be illegitimate, including scams or law enforcement bait. The volume of searches and placement of marijuana retailers in search results is a definitive call for public health leaders to address the previously unrecognized dilemma of online marijuana.

ACKNOWLEDGMENTS
This work was supported by a grant from the National Institutes of Mental Health (R21MH103603). Mr. Caputi acknowledges scholarships from the Joseph Wharton Scholars and the George J. Mitchell Scholarship programs. Dr. Leas acknowledges a training grant from the National Heart, Lung, and Blood Institute (T32HL007034). No other financial disclosures were reported by the authors of this paper.

Source: Online Sales of Marijuana: An Unrecognized Public Health Dilemma – American Journal of Preventive Medicine (ajpmonline.org) March 2018

Damage is caused in several different ways.
BRAIN: Messages are passed from cell to cell (neurons) in the brain by chemicals called neurotransmitters which fit by shape into their own receptor sites on specific cells.
The neurotransmitter, anandamide, an endo-cannabinoid (made in body) whose job is to control by suppression the levels of other neurotransmitters is mimicked and so replaced by a cannabinoid (not made in body) in cannabis called THC (Tetrahydrocannabinol). THC is very much stronger and damps down more forcefully the release of other neurotransmitters. Consequently the total activity of the
brain decreases. Chaos ensues.

Neurotransmitters delivering messages to the hippocampus, the area for learning and memory don’t receive enough stimulation to reach it, so signals are lost for ever.
Academic performance plummets and IQs fall by about 8 points. Neurons can be lost permanently. This is brain damage. No child using cannabis even occasionally will achieve their full potential.
Because signalling is slowed down, reaction times increase. Driving becomes hazardous and fatal accidents are rising in legalised USA states. Alcohol plus cannabis in drivers is 16 times more dangerous.
Since THC is fat-soluble, it stays in cells for weeks, constantly ensuring this decrease in brain activity. In the sixties/seventies the THC content was around 1-3%, now in London only ‘skunk’ at 16-20% THC is available. Professor Sir Robin Murray has said that, ‘users will be in a state of low-grade intoxication most of the time’. The Dopamine neurotransmitter has no receptor sites for anandamide and so THC
doesn’t affect it. But the inhibitory Gaba neurotransmitter has. Gaba normally suppresses dopamine but since it is itself suppressed by THC, levels of dopamine quickly increase. Excess dopamine is found in the brains of psychotics, and even schizophrenics if they have a genetic vulnerability. Anyone taking enough THC at one sitting will suffer a psychotic episode which could become permanent. Aggression, violence, even homicides, suicides and murders have resulted from cannabis-induced psychosis. The first research paper linking THC with psychosis was published in 1845. Cannabis-induced schizophrenia costs the country around £2 billion/year. Some of these mentally ill people will spend the rest of their lives in psychiatric units.
THC also depletes the levels of the ‘happiness’ neurotransmitter Serotonin. This can cause depression which may lead to suicide. THC causes dependence. This will affect 1 in 6 using adolescents and 1 in 9 of the general population. Since THC replaces anandamide, there is no need for its production which reduces and eventually stops so the receptor sites are left empty.
Withdrawal then sets in with irritability, sleeplessness, anxiety, depression, even violence until anandamide production resumes. Rehab specialists have told us that adolescent pot addiction is the most challenging to treat.
Cannabis can also act as a gateway drug – it can ‘prime’ the brain for the use of other drugs. Professor David Fergusson (NZ) in longitudinal studies from birth found that ‘The use of cannabis in late adolescence and early adulthood emerged as the strongest risk factor for later involvement in other illicit drug use’.
THC inhibits the vomiting reflex. If a person has drunk too much alcohol, they are often sick and get rid of it. An overdose of alcohol can kill (respiratory muscles stop working) so using cannabis together with alcohol can be fatal.
The signalling of endo-cannabinoids is crucial in brain development. They guide the formation, survival, proliferation, motility and differentiation of new neurons. THC badly interferes with these essential processes. Chaos ensues among the confused brain signals and a cannabis personality develops. Users can’t think logically. They have fixed opinions and answers, can’t find words, can’t take criticism – it’s always someone else’s fault, and can’t plan their day. Families suffer from their violent mood swings – houses get trashed. Anxiety, panic and paranoia may ensue. At the same time users are lonely, miserable and feel misunderstood.

Respiratory System:
Cannabis smoke has many of the same constituents as tobacco smoke but more of its carcinogens – in cancer terms a joint equals 4/5 cigarettes. More tar is deposited in the lungs and airways. Coughing, wheezing, emphysema, bronchitis and cancers have been seen in the lungs.

Heart:
Heart rates rise and stay high for 3-4 hours after a joint. Heart attacks and strokes have been recorded. Some teenagers had strokes and died after bingeing on cannabis.

Hypothalamus:
The hypothalamus is a region of the brain known to regulate appetite. Endocannabinoids in this area send ‘I’m hungry’ messages. When you take THC, that message is boosted. This is called ‘the munchies’. Nabilone, (synthetic THC) can be used to stimulate the appetite in AIDS patients.

DNA and Reproduction:
THC affects the DNA in any new cells being made in the body. It speeds up the programmed cell death (apoptosis) of our defence white blood cells, so our immune system is diminished. There are also fewer sperm. Infertility and impotence have been reported as far back as the 1990s.
An Australian paper published in July 2016 explains this phenomenon. THC can disrupt the actual process of normal cell division mitosis and meiosis (formation of sperm and eggs). In mitosis, the chromosomes replicate and gather together at the centre of the cell. Protein strands (microtubules) are formed from the ends of the cell to pull half of the chromosomes to each end to form the 2 new cells. Unfortunately THC disrupts microtubule formation. Chromosomes can become isolated, rejoin other bits of chromosome and have other abnormalities. Some will actually be shattered into fragments (chromothripsis).
This DNA damage can also cause cancers. Oncogenes (cancer-causing genes) may be activated, and tumour suppressant genes silenced. Chromosome fragments and abnormal chromosomes are frequently seen in cancerous tissues. This would account for other cancers, leukaemia, brain, prostate, cervix, testes and bladder etc, reported in regions of the body not exposed to the smoke. Pregnant users see a 2-4
fold increase in the number of childhood cancers in their offspring. The DNA damage has also been associated with foetal abnormalities – low birth weight, pre-term birth, spontaneous miscarriage, spina bifida, anencephaly (absence of brain parts), gastroschisis (babies born with intestines outside the body) cardiac defects and shorter limbs. All these defects bear in common an arrest of cell growth and cell migration at critical development stages consistent with the inhibition of mitosis noted with cannabis.
DNA damage at meiosis results in fewer sperm as we have seen. Increased errors in meiosis have the potential for transmission to subsequent generations. The zygote (fertilised egg) death rate rises by 50% after the first division. In infants, birth weight is lower and they may be born addicted. Children may have problems with behaviour and cognitive functions as they grow. Childhood cancers are
more common. Intensive care for newborns doubles. The younger they start using cannabis, the more likely they are to remain immature, become addicted, suffer from mental illnesses or progress to other drugs. Average age of first use is 13. Regular cannabis users have worse jobs, less than average money, downward social mobility, relationship problems and antisocial behaviour.

References:
Cannabis Skunk Website www.cannabisskunksense.co.uk Cannabis: A survey of its
harmful effects by Mary Brett is available on DOWNLOADS. It is a 300+ page report
written in 2006 and kept up to date.

Chromothripsis and epigenomics complete causality criteria for cannabis- and
addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity

Book: Adverse Health Consequencies of Cannabis Use. Jan Ramstrom National Institute of Public Health Sweden www.fhi.se

Source: https://www.cannabisskunksense.co.uk/uploads/site-files/ty,Chromothripsis,CarcinogenicityandFetotoxicity,MR-FMMM.pdf March 2020

• Cannabis is responsible for 91% of drug addiction cases involving teenagers
• Skunk – high-potency herbal cannabis – causing more people to seek treatment 
• Backs up research that skunk is having detrimental impact on mental health

Cannabis is responsible for 91 per cent of cases where teenagers end up being treated for drug addiction, shocking new figures reveal.

Supporters of the drug claim it is harmless, but an official report now warns the ‘increased dominance of high-potency herbal cannabis’ – known as skunk – is causing more young people to seek treatment.

The revelation comes amid growing concerns that universities – and even some public schools – are awash with high-strength cannabis and other drugs.

The findings also back up academic research, revealed in The Mail on Sunday over the past three years, that skunk is having a serious detrimental impact on the mental health of the young. At least two studies have shown repeated use triples the risk of psychosis, with sufferers repeatedly experiencing delusional thoughts. Some victims end up taking their own lives.

The latest UK Focal Point on Drugs report, drawn up by bodies including Public Health England, the Scottish Government and the Home Office, found that:

• Over the past decade, the number of under-18s treated for cannabis abuse in England has jumped 40 per cent – from 9,043 in 2006 to 12,712 in 2017;
• Treatment for all narcotics has increased by 20 per cent – up from 11,618 to 13,961;
• The proportion of juvenile drug treatment for cannabis use is up from four in five cases (78 per cent) to nine in ten (91 per cent);
• There has been a ‘sharp increase’ in cocaine use among 15-year-olds, up 56 per cent from 16,700 in 2014 to 26,200 in 2016.

Last night, Lord Nicholas Monson, whose 21-year-old son Rupert Green killed himself last year after becoming hooked on high-strength cannabis, said: ‘These figures show the extent of the damage that high-potency cannabis wreaks on the young.

‘The big danger for young people – particularly teens – is that their brains can be really messed up by this stuff because they are still developing biologically. If they develop drug-induced psychosis – as Rupert did – the illness can stick for life.’

The large rise in the number of youngsters treated for cannabis abuse comes despite the fact that total usage is falling slightly.

The report concludes: ‘While fewer people are using cannabis, those who are using it are experiencing greater harm.’

Almost all cannabis on Britain’s streets is skunk, which is four times more powerful than types that dominated the market until the early 2000s. It can even trigger hallucinations.

Lord Monson said: ‘We really need Ministers to get a grip and launch a major publicity campaign about the dangers.’ 

Nine in ten teens at drug clinics are being treated for marijuana use  | Daily Mail Online April 2018

• Thousands gathered at crowded ‘420’ rally calling for legalisation of cannabis 
• Possession of the Class B drug carrying maximum jail sentence of five years
• Met Police defended lack of action saying it meant rally passed ‘largely without incident’

It’s a sight that makes a mockery of Britain’s drug laws.

As families relaxed in the warm sunshine, thousands of drug users gathered in a Central London park to smoke cannabis – in full view of the police.

Officers stood by in Hyde Park and watched, smiling, as plumes of pungent smoke filled the air.

Revellers, including some teen-agers, lay sprawled on the grass, confident the police would do nothing at the crowded ‘420’ rally, an annual event which calls for the legalisation of cannabis.

One man said: ‘I’m not that bothered about being arrested. The police will just take it off us – and we’ve got more anyway.’

There were no arrests at Friday’s rally, even though possession of the Class B drug carries a maximum jail sentence of five years.

The shocking failure to enforce the law comes as The Mail on Sunday today reveals nine out of ten teenagers in drug clinics are being treated for cannabis abuse.

A Met Police spokesman last night defended their lack of action, saying its approach to enforcing drug laws ‘meant [the rally] passed off largely without incident’ and was ‘no different from any other day’.

Their leniency is mirrored by new figures showing the police and courts are increasingly going soft on drugs. The number of ‘proven drug law offenders’ plummeted to 102,948 in 2016 – a fall of a quarter in two years, according to the Focal Point on Drugs report.

Of these, ‘the majority were dealt with outside court’, with 41,831 sentenced in court, the rest given a warning or caution. The ‘most common sentence was a fine’, meted out to a third, while a fifth were jailed, including 1,009 for possession and 7,459 for trafficking.

The ‘420’ event is believed to have been named after a group of 1970s Californian youngsters who met after school at 4.20pm to smoke marijuana. The day April 20 has since become an informal festival to celebrate the drug.

Source: Fury as thousands gather to smoke cannabis in Hyde Park and not a SINGLE ONE of them is charged  | Daily Mail Online April 2018

Veterans are twice as likely as non-veterans to die from accidental overdoses involving prescription opioids. In an effort to lower opioid intake, some veterans are turning to hemp products, like CBD oil, to treat chronic pain and PTSD. Now some veterans are saying they want more research and access, reports CBS News correspondent Nancy Cordes. 

They are not your typical lobbyists. They’re veterans whose lives were nearly ruined — first by their injuries, and then by their meds. 

“I was at a higher than likely rate of committing suicide from pain,” Navy veteran Veronica Wayne told lawmakers. She took opioids for 17 years after an airplane maintenance hatch hit her head.

“I basically became a walking zombie,” Wayne said.
 
She tried medical marijuana, but still felt impaired. That’s when she heard about hemp.

“It’ll still kill all the pain symptoms and give you the relief that you need, but you’re not going to feel high,” Wayne said.

Now she uses CBD oil. But, she notes, “You can’t get it from the VA. It’s not, it’s not legal.”

Like marijuana, hemp is derived from the cannabis plant. But hemp does not contain THC, the chemical that makes you high. Still both hemp and marijuana are classified as Schedule 1 controlled substances, restricting the VA and other federally funded entities from conducting research. The American Legion is leading the push to change that.

“Anything that makes a veteran feel better — especially something that’s non-toxic — is something we’re going to support,” said Louis Celli, national director of Veterans Affairs and rehabilitation at the American Legion.
 
Currently hemp products are marketed as unregulated supplements, which makes many doctors reluctant to recommend them.

“We’re not exactly sure how to use them, what the right dose is, how they interact,” said Wayne Jonas, the former director of the NIH office of alternative medicine.

• FDA panel backs marijuana-based drug for childhood seizures

But lawmakers on both sides are pushing to change the law.
 
“I’m actually cautiously optimistic if we get something on the floor, that it will pass,” Rep. Earl Blumenauer, D-Ore., said.

Until then, Army reservist Dale Rider said many of his buddies are wary of the product that he said helps his back pain.
 
“For them, they’re all worried that because it’s so closely related to marijuana, that it could pop up on a drug test randomly,” Rider said.

The industry has a powerful ally in Senate Majority Leader Mitch McConnell, who represents Kentucky, where hemp is seen as a potential cash crop. Last month he introduced a bill in the Senate that has bipartisan support to legalize hemp as an agricultural commodity.

Veterans push lawmakers to legalize hemp products – CBS News April 2018

Foreign gangs are finding that black-market marijuana is profitable even in states that have legalized cannabis.

Source: Foreign cartels embrace home-grown marijuana in pot-legal states (nbcnews.com) May 2018

National Drug Intelligence Center
North Carolina Drug Threat Assessment
April 2003

Marijuana

Marijuana is the most readily available and widely abused drug in North Carolina. Marijuana is abused by individuals of various ages in North Carolina. Outdoor cannabis cultivation is widespread in the state. Indoor cultivation occurs to a lesser extent. Mexican criminal groups, the dominant wholesale distributors of marijuana in the state, transport multiton shipments of Mexico-produced marijuana into North Carolina in tractor-trailers, primarily from Mexico and southwestern states. African American, Caucasian, and Jamaican criminal groups and OMGs also transport marijuana produced in Mexico into North Carolina and distribute wholesale quantities. Caucasian and Mexican criminal groups also distribute wholesale quantities of marijuana produced in large outdoor grows in North Carolina. At the retail level marijuana is distributed by African American, Caucasian, and Hispanic gangs; OMGs; and local independent producers and dealers including students, homemakers, and business people.

Abuse

Marijuana is the most widely abused illicit drug in North Carolina, and the drug is abused by individuals of all ages. According to the 1999 NHSDA, 4.7 percent of North Carolina residents reported having abused marijuana in the 30 days prior to the survey. The same figure was reported nationwide. The survey data also indicate that rates of marijuana abuse are highest among teenagers and young adults. Nearly 14 percent of North Carolina residents aged 18 to 25 surveyed reported having abused marijuana in the past month, while 6.8 percent of residents aged 12 to 17 surveyed reported the same. Of North Carolina residents aged 26 and older, 3.1 percent reported past month marijuana abuse.

The number of marijuana-related treatment admissions in North Carolina ranked second to the number of cocaine-related admissions each year from FY1996 through FY1999. Marijuana-related treatment admissions increased 70 percent from 7,285 in FY1996 to 12,382 in FY1999, according to the North Carolina Department of Health and Human Services. (See Table 3.)

Source: North Carolina Department of Health and Human Services.

According to 2000 ADAM data, 44.2 percent of adult male arrestees tested positive for marijuana. Marijuana abuse was highest among male arrestees under 21 years of age; 84.4 percent of arrestees under 21 tested positive for marijuana.

Availability

Marijuana produced in Mexico or in North Carolina is readily available. Mexico-produced marijuana is relatively inexpensive and has a low THC (tetrahydrocannabinol) content (average 3.3%). According to local law enforcement, in 2001 a pound of Mexico-produced marijuana sold for $600 to $1,000 in North Carolina. A pound of marijuana produced from cannabis cultivated outdoors in North Carolina sold for $600 to $900. In North Carolina cannabis plants cultivated indoors using hydroponic operations usually yield marijuana with a higher THC content that is significantly more expensive. A pound generally sold for $2,400 in 2001.

The number of marijuana-related arrests was dramatically higher in 1999 than in 1994, particularly among juveniles. According to the North Carolina State Bureau of Investigation, juvenile arrests for marijuana possession likewise were significantly higher in 1999 than in 1994.

Source: North Carolina State Bureau of Investigation.
Note: Includes possession or sale/manufacturing.

Source: North Carolina State Bureau of Investigation.
Note: Includes possession.

The amount of marijuana seized in the state increased dramatically from 1998 through 2001. Federal law enforcement authorities in North Carolina seized 801 kilograms of marijuana in 1998, 2,301 kilograms in 1999, 4,885 kilograms in 2000, and 3,826.8 kilograms in 2001, according to FDSS data. Additionally, the number of cannabis plants seized by state and local authorities increased 36 percent from 29,753 in 1999 to 40,464 in 2000.

The number of marijuana-related federal sentences in North Carolina ranked second to cocaine-related federal sentences from FY1996 through FY2000. According to USSC data, the number of marijuana-related federal sentences fluctuated from FY1996 through FY2000, with 113 in FY1996, 72 in FY1997, 79 in FY1998, 124 in FY1999, and 81 in FY2000

Violence

Cannabis growers take extreme measures intended to injure or kill intruders on cultivation sites. Cannabis growers frequently protect their grows by booby trapping them with explosives, trip-wired firing devices, and pits dug in the ground. The perimeters of cultivation sites frequently are littered with shards of glass and wooden boards with upright nails. Cultivation sites may also be guarded by aggressive dogs such as pit bulls. Law enforcement authorities report that weapons, usually firearms, are seized frequently from the homes of cannabis growers. Officials from the Asheville Buncombe Metropolitan Enforcement Group, in response to the NDIC National Drug Threat Survey 2001, report that cannabis growers frequently place animal traps among cannabis plants.

Production

Cannabis cultivation is widespread in North Carolina. Outdoor cannabis cultivation is more common than indoor cultivation because of the state’s long growing season, temperate climate, and rural areas that allow growers to conceal cultivation sites. Cannabis growers frequently use federal forest land, particularly in western North Carolina, to minimize the risk of personal property seizures if the plots are seized by law enforcement. Mexican and Caucasian criminal groups are the primary cultivators of outdoor cannabis. Reporting from law enforcement officials indicates that cannabis cultivation is widespread in areas including the Pisgah and Nantahala National Forests in the western part of the state. Outdoor cultivation sites in North Carolina are larger than before, according to law enforcement authorities. In July 2001 state and local law enforcement authorities seized more than 23,000 cannabis plants, ranging in size from seedlings to 9-foot-tall plants, from a large field that covered nearly 2 acres in Chatham County. This cannabis cultivation site was one of the largest ever seized in North Carolina.

Growers also cultivate high potency cannabis in indoor hydroponic operations. Indoor grows vary in size and number from dozens to several hundred cannabis plants. Indoor cultivation requires the grower to regulate light, heat, humidity, and fertilizer. Caucasian and African American independent producers are the primary cultivators of cannabis using hydroponic techniques.

Transportation

Mexican criminal groups are the dominant transporters of Mexico-produced marijuana into North Carolina. They primarily use tractor-trailers to transport multiton quantities of marijuana concealed among legitimate goods such as produce, furniture, and other items from Mexico and southwestern states. Law enforcement officials report that tractor-trailers carrying 1,000 pounds or more of marijuana are increasingly common. In March 2001 law enforcement authorities in Rowan County seized over 4 tons of marijuana from a tractor-trailer that was destined for a farmhouse in the county. The seizure was one of the largest marijuana seizures in North Carolina history.

Mexican, African American, Caucasian, and Jamaican criminal groups also transport marijuana in private vehicles. These criminal groups transport Mexico-produced marijuana directly from Mexico and southwestern states. They also transport marijuana from Georgia, South Carolina, and Tennessee. Transporters conceal marijuana in luggage or in false compartments and sometimes smear marijuana packages with food or liquid soap to conceal the distinctive odor. In May 2001 a sheriff’s deputy in Harrison County, Mississippi, seized 35 pounds of marijuana from a private vehicle and arrested two Mexican individuals who claimed to be traveling from Edinburg, Texas, to Charlotte. The marijuana was wrapped in packing tape and concealed in the gas tank, which contained two compartments: one for gasoline and one for contraband. In April 2001 a Louisiana state trooper arrested an individual driving a vehicle from Texas to North Carolina and seized 62 pounds of marijuana hidden in luggage in the trunk. The marijuana was wrapped in clear cellophane, smeared with mustard, and wrapped again with fabric softener sheets.

Criminal groups, particularly Jamaican, also transport marijuana into North Carolina on commercial airlines, employing couriers who conceal the drug in their luggage or strap packages of it under their clothing. The DEA San Diego Division reports that San Diego is a principal distribution hub for marijuana produced in Mexico supplied to Jamaican criminal groups in the southeastern United States. Mexican DTOs based in Mexico supply marijuana to Jamaican criminal groups in San Diego who then distribute the drug to other Jamaican criminal groups in North Carolina and other southeastern states. Jamaican criminal groups in North Carolina often falsely market Mexico-produced marijuana as Jamaican marijuana because Jamaican marijuana is reputed to be more potent and is, therefore, more expensive. Marijuana produced in Mexico sells for about $400 per pound in San Diego but sells for as much as $2,400 per pound as Jamaican marijuana in North Carolina.

Mexican, African American, and Caucasian criminal groups also transport marijuana into North Carolina from southwestern states via package delivery services. According to 2000 Operation Jetway data, law enforcement authorities in North Carolina seized at least 19 packages that contained multipound quantities of marijuana. The packages were sent from Texas and California, and most were destined for Charlotte. According to the Charlotte-Mecklenburg Police Department, approximately one-half of the packages were sent to members of Mexican criminal groups, and approximately one-half were sent to members of African American criminal groups.

Mexican, African American, and Caucasian criminal groups also transport marijuana into the state on buses and passenger trains. In December 2000 Davidson County sheriff’s deputies stopped a bus traveling from Texas to North Carolina and seized 80 pounds of marijuana in a duffel bag. None of the passengers admitted to owning the bag. According to law enforcement authorities, the passengers were Mexican migrant workers traveling from Texas to North Carolina for employment.

Unknown quantities of marijuana produced in North Carolina are transported out of the state in private vehicles and via package delivery services into urban and rural areas in Georgia, South Carolina, Tennessee, and Virginia.

Distribution

In North Carolina Mexican criminal groups are the primary wholesale distributors of marijuana produced in Mexico. African American, Caucasian, and Jamaican criminal groups also distribute wholesale quantities of Mexico-produced marijuana. All of these criminal groups distribute marijuana to gang members and local independent dealers; they also distribute some marijuana at the retail level. These criminal groups sell marijuana to dealers of other races and ethnicities; however, in a small number of communities, they distribute marijuana only within their own ethnic group because they distrust outsiders. OMG members sell wholesale quantities to members of smaller motorcycle gangs and female associates who handle retail distribution.

Cannabis growers who cultivate large outdoor plots–usually Caucasian and Mexican criminal groups–sell wholesale quantities of locally produced marijuana to gang members and local independent dealers and occasionally sell retail quantities. Growers who cultivate small amounts of cannabis in their homes or tend small plots–usually Caucasian and African American independent dealers–abuse the drug themselves or sell it to friends, family members, and associates.

At the retail level marijuana is distributed by African American, Caucasian, and Hispanic gangs; OMGs; and local independent producers and dealers including students, homemakers, and businesspeople. Law enforcement authorities report that marijuana is sold at various locations such as open-air drug markets; parking lots; bars and nightclubs; college, high school, and middle school campuses; and businesses and private homes. Law enforcement authorities report that high school students, in particular, are becoming increasingly involved in retail marijuana distribution on and near school grounds. In April 2001, law enforcement officers in Chapel Hill arrested a high school student who had concealed small plastic bags of marijuana in a sock that he had hidden in his pants. Law enforcement officers report that the student intended to sell the marijuana to other students on school grounds.

Marijuana – North Carolina Drug Threat Assessment (justice.gov)