2023 June

Abstract

Background

Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.

Methods and findings

This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3–54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34–0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration.

Conclusions

We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Author summary

Why was this study done?

  • High numbers of people who use (illicit) drugs (PWUD) experience chronic pain, and previous research shows that illicit use of opioids (e.g., heroin use, non-prescribed use of painkillers) is a common pain management strategy in this population.
  • Previous research has suggested that some patients might substitute opioids (i.e., prescription painkillers) with cannabis (i.e., marijuana) to treat pain.
  • Research into cannabis as a potential substitute for illicit opioids among PWUD is needed given the high risk of opioid overdose in this population.
  • We conducted this study to understand if cannabis use is related to illicit opioid use among PWUD who report living with chronic pain in Vancouver, Canada, where cannabis is abundant and the rate of opioid overdose is at an all-time high.

What did the researchers do and find?

  • Using data from 2 large studies of PWUD in Vancouver, Canada, we analyzed information from 1,152 PWUD who were interviewed at least once and reported chronic pain at some point between June 2014 and December 2017.
  • We used statistical modelling to estimate the odds of daily opioid use for (1) daily and (2) occasional users of cannabis relative to non-users of cannabis, holding other factors (e.g., sex, race, age, use of other drugs, pain severity) equal.
  • For participants who reported cannabis use, we also analyzed their responses to a question about why they were using cannabis (e.g., for intoxication, for pain relief)
  • We found that people who used cannabis every day had about 50% lower odds of using illicit opioids every day compared to cannabis non-users. People who reported occasional use of cannabis were not more or less likely than non-users to use illicit opioids on a daily basis. Daily cannabis users were more likely than occasional cannabis users to report a number of therapeutic uses of cannabis including for pain, nausea, and sleep.

What do these findings mean?

  • Although more experimental research (e.g., randomized controlled trial of cannabis coupled with low-dose opioids to treat chronic pain among PWUD) is needed, these findings suggest that some PWUD with pain might be using cannabis as a strategy to alleviate pain and/or reduce opioid use.

Introduction

Opioid-related morbidity and mortality continue to rise across Canada and the United States. In many regions, including Vancouver, Canada—where drug overdoses were declared a public health emergency in 2016—the emergence of synthetic opioids (e.g., fentanyl) in illicit drug markets has sparked an unprecedented surge in death. The overdose crisis is also the culmination of shifting opioid usage trends (i.e., from initiating opioids via heroin to initiating with pharmaceutical opioids) that can be traced back, in part, to the over-prescription of pharmaceutical opioids for chronic non-cancer pain.

Despite this trend of liberal opioid prescribing, certain marginalized populations experiencing high rates of pain, including people who use drugs (PWUD), lack access to adequate pain management through the healthcare system. Under- or untreated pain in this population can promote higher-risk substance use, as patients may seek illicit opioids (i.e., unregulated heroin or counterfeit/diverted pharmaceutical opioids) to manage pain. In Vancouver, this practice poses a particularly high risk of accidental overdose, as estimates show that almost 90% of drugs sold as heroin are contaminated with synthetic opioids, such as fentanyl. Another less-examined pain self-management strategy among PWUD is the use of cannabis. Unlike illicit opioids and illicit stimulants, the cannabis supply (unregulated or regulated) has not been contaminated with fentanyl, and cannabis is not known to pose a direct risk of fatal overdose. As a result, cannabis has been embraced by some, including emerging community-based harm reduction initiatives in Vancouver, as a possible substitute for opioids in the non-medical management of pain and opioid withdrawal. Further, clinical evidence supports the use of cannabis or cannabinoid-based medications for the treatment of certain types of chronic non-cancer pain (e.g., neuropathic pain).

As more jurisdictions across North America introduce legal frameworks for medical or non-medical cannabis use, ecological studies have provided evidence to suggest that states providing access to legal cannabis experience population-level reductions in opioid use, opioid dependence, and fatal overdose. However, these state-level trends do not necessarily represent changes within individuals, highlighting a critical need to conduct individual-level research to better understand whether cannabis use is associated with reduced use of opioids and risk of opioid-related harms, particularly among individuals with pain. Of particular interest is a possible opioid-sparing effect of cannabis, whereby a smaller dose of opioids provides equivalent analgesia to a larger dose when paired with cannabis. Although this effect has been identified in pre-clinical studies, much of the current research in humans is limited to patient reports of reductions in the use of prescription drugs (including opioids) as a result of cannabis use. However, a recent study among patients on long-term prescription opioid therapy produced evidence to counter the narrative that cannabis use leads to meaningful reductions in opioid prescriptions or dose. These divergent findings confirm an ongoing need to understand this complex issue. To date, there is a lack of research from real-world settings exploring the opioid-sparing potential of cannabis among high-risk individuals who may be engaging in frequent illicit opioid use to manage pain. We therefore sought to examine whether frequency of cannabis use was related to frequency of illicit opioid use among PWUD who report living with chronic pain in Vancouver, Canada, the setting of an ongoing opioid overdose crisis.

Methods

Study sample

Data for this study were derived from 2 ongoing open prospective cohort studies of PWUD in Vancouver, Canada. The Vancouver Injection Drug Users Study (VIDUS) consists of HIV-negative people who use injection drugs. The AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS) consists of people living with HIV who use drugs. The current study, nested within these cohorts, was designed as part of a larger doctoral research project (SL) examining cannabis use and access among PWUD in the context of changing cannabis policy and the ongoing opioid overdose crisis. The analysis plan for this study is provided in S1 Text. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies (S1 Checklist).

Recruitment for the cohort studies has been ongoing since 1996 (VIDUS) and 2005 (ACCESS) through extensive street outreach in various areas across Vancouver’s downtown core, including the Downtown Eastside (DTES), a low-income neighbourhood with an open illicit drug market and widespread marginalization and criminalization. To be eligible for VIDUS, participants must report injecting drugs in the previous 30 days at enrolment. To be eligible for ACCESS, participants must report using an illicit drug (other than or in addition to cannabis, which was a controlled substance under Canadian law until October 17, 2018) in the previous 30 days at enrolment. For both cohorts, HIV serostatus is confirmed through serology. Other eligibility requirements include being aged 18 years or older, residing in the Metro Vancouver Regional District, and providing written informed consent. Aside from HIV-disease-specific assessments, all study instruments and follow-up procedures are harmonized between the 2 studies to facilitate combined data analysis and interpretation.

At study enrolment, participants complete an interviewer-administered baseline questionnaire. Every 6 months thereafter, participants are eligible to complete a follow-up questionnaire. The questionnaires elicit information on socio-demographic characteristics, lifetime (baseline) and past-6-month (baseline, follow-up) patterns of substance use, risk behaviours, healthcare utilization, social and structural exposures, and other health-related factors. Nurses collect blood samples for HIV testing (VIDUS) or HIV clinical monitoring (ACCESS) and hepatitis C virus serology, providing referrals to appropriate healthcare services as needed. Participants are provided a Can$40 honorarium for their participation at each study visit.

Ethics statement

Ethics approval for this study was granted by the University of British Columbia/Providence Health Care Research Ethics Board (VIDUS: H14-01396; ACCESS: H05-50233). Written informed consent was obtained from all study participants.

Measures

To examine the use of illicit opioids and cannabis for possible ad hoc management of pain among PWUD, we restricted the study sample to individuals experiencing major or persistent pain. Beginning in follow-up period 17 (i.e., June 2014), the following question was added to the study questionnaire: “In the last 6 months, have you had any major or persistent pain (other than minor headaches, sprains, etc.)?” We included all observations from participants beginning at the first follow-up interview in which they reported chronic pain. For example, a participant who responded “no” to the pain question at follow-up 17 and “yes” at follow-up 18 would be included beginning at follow-up 18. For the purpose of these analyses, this first follow-up period with a pain report is considered the “baseline” interview.

The outcome of interest was frequent use of illicit opioids, defined as reporting daily (once or more per day) non-medical use of heroin or pharmaceutical opioids (diverted, counterfeit, or not-as-prescribed use) by injection or non-injection (i.e., smoking, snorting, or oral administration) in the previous 6 months. This outcome was captured through 4 different multipart questions based on class of opioid (i.e., heroin and pharmaceutical opioids) and mode of administration (i.e., injection and non-injection). For example, at each 6-month period, injection heroin use was assessed through the question: “In the last 6 months, when you were using, which of the following injecting drugs did you use, and how often did you use them?” Respondents were provided a list of commonly injected drugs, including heroin, and were asked to estimate their average frequency of injection in the past 6 months according to the following classifications: <1/month, 1–3/month, 1/week, 2–3/week, ≥1/day. An identical question for non-injection drugs assessed the frequency of non-injection heroin use. Pharmaceutical opioid injection was assessed through the question “In the past 6 months, have you injected any of the following prescription opioids? If so, how often did you inject them?” Participants were provided a list of pharmaceutical opioids with corresponding pictures for ease of identification. The question was repeated for non-injection use of pharmaceutical opioids, and the frequency categories were identical to those listed above. Using frequency categorizations from these 4 questions, participants who endorsed past-6-month daily injection or non-injection of heroin or pharmaceutical opioids were coded as “1” for the outcome (i.e., daily illicit opioid use) for that follow-up period. The main independent variable was cannabis use, captured through the question “In the last 6 months, have you used marijuana (either medical or non-medical) for any reason (e.g., to treat a medical condition or for a non-medical reason, like getting high)?” Those who responded “yes” were also asked to estimate their average past-6-month frequency of use according to the frequency categories described above. Frequency was further categorized as “daily” (i.e., ≥1/day), “occasional” (i.e., <1/month, 1–3/month, 1/week, 2–3/week), and “none” (no cannabis use; reference category). Sections of the questionnaire used for sample restriction and main variable building are provided in S2 Text.

We also considered several socio-demographic, substance use, and health-related factors with the potential to confound the association between cannabis use and illicit opioid use. Secondary socio-demographic variables included in this analysis were sex (male versus female), race (white versus other), age (in years), employment (yes versus no), incarceration (yes versus no), homelessness (yes versus no), and residence in the DTES neighbourhood (yes versus no). We considered the following substance use patterns: daily crack or cocaine use (yes versus no), daily methamphetamine use (yes versus no), and daily alcohol consumption (yes versus no). Health-related factors that were hypothesized to bias the association between cannabis and opioid use were enrolment in opioid agonist treatment (i.e., methadone or buprenorphine/naloxone; yes versus no), HIV serostatus (HIV-positive versus HIV-negative), prescription for pain (including prescription opioids; yes versus no), and average past-week pain level (mild–moderate, severe, or none). The pain variable was self-reported using a pain scale ranging from 0 (no pain) to 10 (worse possible pain). We used 3 as the cut-point for mild–moderate pain and 7 as the cut-point for moderate–severe pain. Although there is no universal standard for pain categorization, these cut-points are common and have been validated in other pain populations. Due to low cell count for mild pain (scores 1–3), we collapsed this variable with moderate pain (4–6) to create the mild–moderate category. With the exception of sex and race, all variables are time-updated and refer to behaviours and exposures in the 6-month period preceding the interview. All variables except HIV status were derived through self-report. As data for the present study were derived from 2 large cohort studies with broader objectives of monitoring changing health and substance use patterns in the community, the study participants and interviewers were blinded to the objective of this particular study.

Statistical analysis

We explored differences in characteristics at baseline according to daily cannabis use status (versus occasional/none) using chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Then, we estimated bivariable associations between each independent variable and the outcome, daily illicit opioid use, using generalized linear mixed-effects models (GLMMs) with a logit-link function to account for repeated measures within individuals over time. Next, we built a multivariable GLMM to estimate the adjusted association between frequency of cannabis use and illicit opioid use. We used the least absolute shrinkage and selection operator (LASSO) approach to determine which variables to include in the multivariable model. This method uses a tuning parameter to penalize the model based on the absolute value of the magnitude of coefficients (i.e., L1 regularization), shrinking some coefficients down to 0 (i.e., indicating their removal from the multivariable GLMM). Four-fold cross-validation was used to determine the optimal value of the tuning parameter. GLMMs were estimated using complete cases (98.6%–100% of observations for bivariable estimates; 99.0% of observations for multivariable estimates).

In the most recent follow-up period (June 1, 2017, to December 1, 2017), participants who reported any cannabis use in the previous 6-month period were eligible for the follow-up question: “Why did you use it?” Respondents could select multiple options from a list of answers or offer an alternative reason under “Other”. These data were analyzed descriptively, and differences between at least daily and less than daily cannabis users were analyzed using a chi-squared test, or Fisher’s test for small cell counts.

All analyses were performed in RStudio (version 1.1.456; R Foundation for Statistical Computing, Vienna, Austria). All p-values are 2-sided.

Results

Between June 1, 2014, and December 1, 2017, 1,489 participants completed at least 1 study visit and were considered potentially eligible for these analyses. Of them, 13 participants were removed due to missing data on the fixed variable for race (n = 9), no response to the pain question (n = 1), or multiple interviews during a single follow-up period (n = 3). Of the remaining 1,476 participants, 1,152 (78.0%) reported major or persistent pain during at least one 6-month follow-up period and were included in this analysis. We considered all observations from these individuals beginning from the first report of chronic pain, yielding 5,350 study observations, equal to 2,676.5 person-years of observation. There were 424 (36.8%) female participants in the analytic sample, and the median age at the earliest analytic interview was 49.3 years (IQR 42.3–54.9).

Over the study period, a total of 410 (35.6%) respondents reported daily and 557 (48.4%) reported occasional cannabis use throughout at least 1 of the 6-month follow-up periods; 455 (39.5%) reported daily illicit opioid use throughout at least 1 of the 6-month follow-up periods. At baseline (i.e., the first interview in which chronic pain was reported), 583 (50.6%) participants were using cannabis either occasionally (n = 322; 28.0%) or daily (n = 261; 22.7%), and 269 (23.4%) were using illicit opioids daily. At baseline, 693 (60.2%) participants self-reported a lifetime chronic pain diagnosis including bone, mechanical, or compressive pain (n = 347; 50.1%); inflammatory pain (n = 338; 48.8%); neuropathic pain (n = 129; 18.6%); muscle pain (n = 54; 7.8%); headaches/migraines (n = 41; 5.9%); and other pain (n = 53; 7.6%).

Table 1 provides a summary of baseline characteristics of the sample stratified by daily cannabis use status (yes versus no). Daily cannabis use at baseline was significantly more common among men (odds ratio [OR] 1.76, 95% 95% CI 1.30–2.38, p < 0.001) and significantly less common among those who used illicit opioids daily (OR 0.54, 95% CI 0.37–0.77, p < 0.001).

Discussion

In this longitudinal study examining patterns of past-6-month frequency of cannabis and illicit opioid use, we found that the odds of daily illicit opioid use were lower (by about half) among those who reported daily cannabis use compared to those who reported no cannabis use. However, we observed no significant association between occasional cannabis use and daily opioid use, suggesting that there may be an intentional therapeutic element associated with frequent cannabis use. This is supported by cross-sectional data from the sample in which certain reasons for cannabis use were observed to differ according to cannabis use frequency. Specifically, daily users reported more therapeutic motivations for cannabis use (including to address pain, stress, nausea, mental health, or symptoms of HIV or antiretroviral therapy, or to improve sleep) than occasional users, and non-medical motivations—although common among all users—were not more likely to be reported by daily users. Together, our findings suggest that PWUD experiencing pain might be using cannabis as an ad hoc (i.e., improvised, self-directed) strategy to reduce the frequency of opioid use.

A recent study analyzed longitudinal data from a large US national health survey and found that cannabis use increases, rather than decreases, the risk of future non-medical prescription opioid use in the general population, providing important evidence to challenge the hypothesis that increasing access to cannabis facilitates reductions in opioid use. The findings of our study reveal a contrasting relationship between cannabis use and frequency of opioid use, possibly due to inherent differences in the sampled populations and their motivations for using cannabis. Within the current study population, poly-substance use is the norm; HIV and related comorbidities are common; and pain management through prescribed opioids is often denied, increasing the likelihood of non-medical opioid use for a medical condition. Furthermore, our study is largely focused on this relationship in the context of pain (i.e., by examining individuals with self-reported pain and accounting for intensity of pain). Our findings align more closely with those of a recent study conducted among HIV-positive patients living with chronic pain, in which the authors found that patients who reported past-month cannabis use were significantly less likely to be taking prescribed opioids. While this finding could have resulted from prescription denial associated with the use of cannabis (or any illicit drug), we show that daily cannabis users in this setting were slightly more likely to have been prescribed a pain medication at baseline, and adjusting for this factor in a longitudinal multivariable model did not negate the significant negative association of frequent cannabis use with frequent illicit opioid use.

The idea of cannabis as an adjunct to, or substitute for, opioids in the management of chronic pain has recently earned more serious consideration among some clinicians and scientists. A growing number of studies involving patients who use cannabis to manage pain demonstrate reductions in the use of prescription analgesics alongside favourable pain management outcomes. For example, Boehnke et al. found that chronic pain patients reported a 64% mean reduction in the use of prescription opioids after initiating cannabis, alongside a 45% mean increase in self-reported quality of life. Degenhardt et al. found that, in a cohort of Australian patients on prescribed opioids for chronic pain, those using cannabis for pain relief (6% of patients at baseline) reported better analgesia from adjunctive cannabis use (70% average pain reduction) than opioid use alone (50% average reduction). However, more recent high-quality research has presented findings to question this narrative. For example, in the 4-year follow-up analysis of the above Australian cohort of pain patients, no significant temporal associations were observed between cannabis use (occasional or frequent) and a number of outcomes including prescribed opioid dose, pain severity, opioid discontinuation, and pain interference. Thus, several other explanations for our current results, aside from an opioid-sparing effect, are worthy of consideration.

We chose to include individuals with chronic pain regardless of their opioid use status to avoid exclusion of individuals who may have already ceased illicit opioid use at baseline, as these individuals may reflect an important subsample of those already engaged in cannabis substitution. On the other hand, there may be important characteristics, unrelated to pain, among regular cannabis users in this study that predispose them to engage in less frequent or no illicit opioid use at the outset. We attempted to measure and control for these factors, but we cannot rule out the possibility of a spurious connection. For example, individuals in this cohort who are consuming cannabis daily for therapeutic purposes may simply possess greater self-efficacy to manage health problems and control their opioid use. However, it is notable that our finding is in line with a previous study demonstrating that cannabis use correlates with lower frequency of illicit opioid use among a sample of people who inject drugs in California, all of whom used illicit opioids. Our study builds on this work by addressing chronic pain, obtaining detailed information on motivations for cannabis use, and examining longitudinal patterns.

We observed that daily cannabis users endorsed intentional use of cannabis for a range of therapeutic purposes that may influence pain and pain interference. After pain, insomnia (43%) and stress (42%) were the second and third most commonly reported motivations for therapeutic cannabis use among daily cannabis users. The inability to fall asleep and the inability stay asleep are common symptoms of pain-causing conditions, and experiencing these symptoms increases the likelihood of opioid misuse among chronic pain patients. The relationship between sleep deprivation and pain is thought to be bidirectional, suggesting that improved sleep management may improve pain outcomes. Similarly, psychological stress (particularly in developmental years) is a well-established predictor of chronic pain and is also likely to result from chronic pain. Thus, another possible explanation for our finding is that cannabis use substitutes for certain higher-risk substance use practices in addressing these pain-associated issues without necessarily addressing the pain itself.

Notably, our findings are consistent with emerging knowledge of the form and function of the human endocannabinoid and opioid receptor systems. The endogenous cannabinoid system, consisting of receptors (cannabinoid type 1 [CB1] and type 2 [CB2]) and modulators (the endocannabinoids anandamide and 2-arachidonoylglycerol), is involved in key pain processing pathways. The co-localization of endocannabinoid and μ-opioid receptors in brain and spinal regions involved in antinociception, and the modification of one system’s nociceptive response via modulation of the other, has raised the possibility that the phytocannabinoid tetrahydrocannabinol (THC) might interact synergistically with opioids to improve pain management. A recent systematic review and meta-analysis found strong evidence of an opioid-sparing effect for cannabis in animal pain models, but little evidence from 9 studies in humans. However, the authors of the meta-analysis identified several important limitations potentially preventing these studies in humans from detecting an effect, including low sample sizes, single doses, sub-therapeutic opioid doses, and lack of placebo. Since then, Cooper and colleagues have published the results of a double-blind, placebo-controlled, within-subject study among humans in which they found that pain threshold and tolerance were improved significantly when a non-analgesic dose of an opioid was co-administered with a non-analgesic dose of cannabis. Suggestive of a synergistic effect, these findings provide evidence for cannabis’s potential to lower the opioid dose needed to achieve pain relief.

Finally, there is pre-clinical and pilot clinical research to suggest that cannabinoids, particularly cannabidiol (CBD), may play a role in reducing heroin cue-induced anxiety and cravings and symptoms of withdrawal. Although preliminary, this research supports the idea that cannabis may also be used to stabilize individuals undergoing opioid withdrawal, as an adjunct to prescribed opioids to manage opioid use disorder, or as a harm reduction strategy. Although this evidence extends beyond chronic pain patients, it warrants consideration here given the shared history of illicit substance use amongst the study sample. It is not clear what role harm reduction or treatment motivations may have played in the current study since daily and occasional users did not differ significantly in reporting cannabis use as a strategy to reduce or treat other substance use. The phenomenon of using cannabis as a tool to reduce frequency of opioid injection has been highlighted through qualitative work in other settings, but further research is needed to determine whether this pattern is widespread enough to produce an observable effect. Clinical trials that can randomize participants to a cannabis intervention will be critical for establishing the effectiveness of cannabis both for pain management and as an adjunctive therapy for the management of opioid use disorder. Such trials would begin to shed light on whether the current finding could be causal, what the underlying mechanisms might be, and how to optimize cannabis-based interventions in clinical or community settings.

There are several important limitations to this study that should be taken into consideration. First, the cohorts are not random samples of PWUD, limiting the ability to generalize these findings to the entire community or to other settings. The older median age of the sample should especially be taken into consideration when interpreting these findings against those from other settings. Second, as discussed above, we cannot rule out the possibility of residual confounding. Third, aside from HIV serostatus, we relied on self-report for all variables, including substance use patterns. Previous work shows PWUD self-report to be reliable and valid against biochemical verification, and we have no reason to suspect that responses about the outcome would differ by cannabis use status, especially since this study was nested within a much larger cohort study on general substance use and health patterns within the community. Major or persistent pain, which qualified respondents for inclusion in this study, was also self-reported. Our definition for chronic pain is likely to be more sensitive than other assessments of chronic pain (e.g., clinical diagnoses or assessments that capture length of time with pain). Although more than half (60%) of the sample reported ever having been diagnosed with a pain condition, it is possible that some of the included respondents would not have met criteria for a formal chronic pain diagnosis. Finally, we did not collect information on the type of cannabis, mode of administration, cannabinoid content (e.g., percent THC:percent CBD), or dose during the study period. Future research will need to address these gaps to provide a more detailed picture of the instrumental use of cannabis for pain and other health concerns among PWUD.

Conclusions

In conclusion, we found evidence to suggest that frequent use of cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain in Vancouver. The findings of this study have implications for healthcare and harm reduction service providers. In chronic pain patients with complex socio-structural and substance use backgrounds, cannabis may be used as a means of treating health problems or reducing substance-related harm. In the context of the current opioid crisis and the recent rollout of a national regulatory framework for cannabis use in Canada, frequent use of cannabis among PWUD with pain may play an important role in preventing or substituting frequent illicit opioid use. PWUD describe a wide range of motivations for cannabis use, some of which may have stronger implications in the treatment of pain and opioid use disorder. Patient–physician discussions of these motivations may aid in the development of a treatment plan that minimizes the likelihood of high-risk pain management strategies, yet there remains a clear need for further training and guidance specific to medical cannabis use for pain management.

Source: Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis – PubMed (nih.gov) November 2019

Filed under: Cannabis/Marijuana,Drug use-various effects,Drug use-various effects on foetus, babies, children and youth,Heroin/Methadone,Methamphetamine/GHB/Hallucinogens/Oxycodone,Prescription Drugs,Synthetics :

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

Filed under: Brain and Behaviour,Cannabis/Marijuana,Drug use-various effects,Drug use-various effects on foetus, babies, children and youth,Global Drug Legalisation Efforts,Health,Legal Sector,Marijuana and Medicine,Nicotine,Social Affairs :

Abstract

Purpose of review 

Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic.

Recent findings 

The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants.

Summary 

With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.

Source: Effects of marijuana on reproductive health: preconception a… : Current Opinion in Endocrinology, Diabetes and Obesity (lww.com) December 2021

Filed under: Cannabis/Marijuana,Drug use-various effects on foetus, babies, children and youth,Health :

Opioid pain relievers are most often prescribed following surgery or to treat cancer pain — situations less common to young people.

However, there are situations or ailments for which opioids may be recommended for your child. These include accidental injury, after oral surgery to remove wisdom teeth, sickle cell disease and other pediatric chronic pain conditions.

Should a health care provider recommend or prescribe an opioid for your child, there are important questions to ask, risks to be aware of and safety precautions to take.

What are some common opioid pain relievers?

  • Hydrocodone (Zohydro)
  • Hydrocodone + Acetaminophen (Vicodin)
  • Oxycodone (Oxycontin, Roxicodone)
  • Oxycodone + Acetaminophen (Percocet)
  • Codeine, Tylenol with Codeine
  • Morphine
  • Fentanyl
  • Tramadol

There are also non-opioid pain relievers (gabapentin, for example) with potential for misuse and abuse, but much lower than that of opioids.

Why is the misuse of opioids so dangerous?

Opioid pain relievers are powerful drugs — very similar to heroin in their chemical makeup and habit-forming by their very nature. This is why the U.S. Centers for Disease Control and Prevention (CDC) strongly recommends against the prescribing of opioids for long-term treatment of chronic pain. Even for treatment of short-term pain, opioid pain relievers should only be prescribed and taken sparingly.

The risk of addiction grows when the patient is a teen or young adult because their brains are still developing and biologically predisposed to experimentation. Suppose your teen or young adult is prescribed an opioid. In that case, you or another caregiver should control the medication, dispense it only as prescribed and monitor closely for signs of misuse or growing dependence.

In addition to the danger of dependence, misuse of opioids can cause dramatic increases in blood pressure and heart rate, organ damage, difficulty breathing, seizures and even death.

What questions should you ask if an opioid is recommended?

Is a prescription opioid necessary?

Ask about alternatives. An over-the-counter (OTC) pain reliever like acetaminophen (e.g., Tylenol) in combination with a non-steroidal anti-inflammatory drug (NSAID) might be just as effective. You can ask about exploring treatments like physical therapy, acupuncture, biofeedback or massage for chronic pain.

What is the quantity and duration of the prescription?

How many pills are being prescribed, and over what period of time?  Is it necessary to prescribe this quantity of pills?

What are the risks of misuse?

The prescriber should be able to answer this question for any drug being prescribed.

Should my child be screened to determine their risk of substance use disorder (SUD) before being prescribed this medication?

If not, why not? Common risk factors include co-occurring mental health disorders such as depression or ADHD, as well as a family history of addiction or a recent trauma such as a death in the family or a divorce.

What if an opioid has been prescribed?

Safeguard medication at home

Don’t just leave it in a medicine cabinet where anyone — family or visitors — can access it, and dispose of any unused medication. For proper disposal, look for a local “takeback” event. If none exist, mix the medication with coffee grounds or other unpleasant garbage and throw it out.

Supervise the dispensing of medication

Keep a count of pills to be sure they are being taken as prescribed, and clearly document when the prescription was filled and when a refill will be needed. Be suspicious of any missing medication.

Communicate the risks of misuse

Make sure your child understands the risks associated with prescription pain relievers, and be very clear that their medication, as with any prescription, is not to be shared with others.

Monitor your child’s levels of pain

Communicate regularly with your child about the level of pain they’re feeling, making sure it’s diminishing with time. Stay alert for any signs that your child is growing dependent on the medication.

What are some signs of misuse or dependence?

If your child is asking for pain medication more frequently than prescribed, or they’re insistent on refilling the prescription, this is a cause for concern. Consult the prescriber to help determine whether pain is going beyond its expected range.

Adverse effects of opioids — which could be a sign of misuse — include drowsiness, nausea, constipation, slowed breathing and slurred speech.

Signs of withdrawal — which would occur if your child has become dependent on an opioid and then stopped taking it — include anxiety, irritability, loss of appetite, craving for the drug, runny nose, sweating, vomiting and diarrhea.

If you’re concerned that your child may be dependent, consult the prescriber, who may in turn consult with a pain specialist. They should consider having a substance use counselor complete an assessment that reviews the extent of your child’s drug and alcohol use, their mental and physical health as well as personal, medical and family history.

Source: When Opioid Pain Relievers Are Prescribed For Your Child: What You Should Know – Partnership to End Addiction (drugfree.org)  March 2019

Filed under: Drug use-various effects on foetus, babies, children and youth,Methamphetamine/GHB/Hallucinogens/Oxycodone,Prescription Drugs :

Abstract
Aim: To evaluate the effectiveness of an online school-based prevention program for ecstasy (MDMA) and new psychoactive substances (NPS).

Design: Cluster randomized controlled trial with two groups (intervention and control).

Setting: Eleven secondary schools in Australia.

Participants: A total of 1126 students (mean age: 14.9 years).

Intervention: The internet-based Climate Schools: Ecstasy and Emerging Drugs module uses cartoon storylines to convey information about harmful drug use. It was delivered once weekly, during a 4-week period, during health education classes. Control schools received health education as usual.

Measurement: Primary outcomes were self-reported intentions to use ecstasy and NPS at 12 months. Secondary outcomes were ecstasy and NPS knowledge and life-time use of ecstasy and NPS. Surveys were administered at baseline, post-intervention and 6 and 12 month post-baseline.

Findings: At 12 months, the proportion of students likely to use NPS was significantly greater in the control group (1.8%) than the intervention group [0.5%; odds ratio (OR) = 10.17, 95% confidence interval (CI) = 1.31-78.91]. However, students’ intentions to use ecstasy did not differ significantly between groups (control = 2.1%, intervention = 1.6%; OR = 5.91, 95% CI = 1.01-34.73). There was a significant group difference in the change from baseline to post-test for NPS knowledge (β = -0.42, 95% CI = -0.62 to -0.21, Cohen’s d = 0.77), with controls [mean = 2.78, standard deviation (SD = 1.48] scoring lower than intervention students (mean = 3.85, SD = 1.49). There was also evidence of a significant group difference in ecstasy knowledge at post-test (control: mean = 9.57, SD = 3.31; intervention: mean = 11.57, SD = 3.61; β = -0.54, 95% CI = -0.97 to -0.12, P = 0.01, d = 0.73).

Conclusions: The Climate Schools: Ecstasy and Emerging Drugs module, a universal online school-based prevention program, appeared to reduce students’ intentions to use new psychoactive substances and increased knowledge about ecstasy and new psychoactive substances in the short term.

Keywords: Adolescents; ecstasy; internet; new psychoactive substance; prevention.

Source: https://pubmed.ncbi.nlm.nih.gov/26880476/ April 2016

Filed under: Ecstasy,Internet,Prevention and Intervention,Synthetics,Youth :

Click here to view the video

Source: Chronic State from DrugFree Idaho, Inc. on Vimeo. July 2018

Filed under: Cannabis/Marijuana,Drug use-various effects,Global Drug Legalisation Efforts :

Abstract

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB1Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB1Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

Source: Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity | Science May 2007

Filed under: Cannabis/Marijuana,Drug use-various effects on foetus, babies, children and youth :

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

Filed under: Cannabis/Marijuana,Drug use-various effects,Health :

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

Search results
Retailer First link First page Second page Total
Yes 8 (67) 66 (50) 48 (32) 114 (41)
No 4 (33) 65 (50) 100 (68) 165 (59)

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

Filed under: Cannabis/Marijuana,Economic,Global Drug Legalisation Efforts,Internet,Legal Sector,Political Sector,Social Affairs,USA :

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

Filed under: Brain and Behaviour,Cannabis/Marijuana,Drug use-various effects,Drug use-various effects on foetus, babies, children and youth,Health :

Abstract

The aim was to examine cross-sectional association between moderate alcohol consumption and total brain volume in a cohort of participants in early middle-age, unconfounded by age-related neuronal change. 353 participants aged 39 to 45 years reported on their alcohol consumption using the AUDIT-C measure. Participants with alcohol abuse were excluded. Brain MRI was analyzed using a fully automated method. Brain volumes were adjusted by intracranial volume expressed as adjusted total brain volume (aTBV). AUDIT-C mean of 3.92 (SD 2.04) indicated moderate consumption. In a linear regression model, alcohol consumption was associated with smaller aTBV (B = – 0.258, p < .001). When sex and current smoking status were added to the model, the association remained significant. Stratified by sex, the association was seen in both males (B = – 0.258, p = 0.003) and females (B = – 0.214, p = 0.011). Adjusted for current smoking, the association remained in males (B = – 0.268, p = 0.003), but not in females. When alcohol consumption increased, total brain volume decreased by 0.2% per one AUDIT-C unit already at 39-45 years of age. Moderate alcohol use is associated with neuronal changes in both males and females suggesting health risks that should not be overlooked.

Figure 1 

Association between AUDIT-C and aTBV. Association between alcohol consumption (AUDIT-C as a continuous variable) and total brain volume adjusted for intracranial volume in males and females. Points in the plot have been jittered to improve visibility of single cases.
Source: Moderate alcohol use is associated with decreased brain volume in early middle age in both sexes – PubMed (nih.gov) August 2020
Filed under: Alcohol,Brain and Behaviour,Health :

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