Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

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

Effects of repeated morphine deprivation on operant responding in rats.

These studies determined the effects of repeated morphine deprivation on behavior maintained by various reinforcers in the rat. A morphine dosing schedule was designed and characterized to establish and maintain dependence while allowing for repeated observation of behavior during morphine deprivation-induced withdrawal. Self-administration of the mu-opioid agonist remifentanil was assessed in nondependent (morphine-naive) rats and compared with self-administration in morphine dependent and deprived groups. Morphine deprivation was found to enhance remifentanil self-administration. The selectivity of this effect was assessed by evaluating the effects of morphine deprivation on behavior maintained by cocaine and two food reinforcers. Deprivation did not alter cocaine self-administration; however, deprivation did enhance behavior maintained by both food reinforcers. The increase in food-maintained behavior observed in the deprived group was likely due to morphine induced food deprivation and consequent weight loss throughout the experiment. Finally, to further characterize morphine deprivation-induced changes on the reinforcing effectiveness of remifentanil, economic demand was determined in dependent and nondependent groups of rats. Compared with nondependent rats, morphine-deprived rats demonstrated less elastic demand for remifentanil indicating that deprivation increased its reinforcing effectiveness. These studies provide evidence that morphine dependence and deprivation enhances the reinforcing properties of remifentanil.Ph.D.Health and Environmental SciencesPharmacologyPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126394/2/3253247.pd

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective

Recent policy changes have led to significant increases in the use of cannabis for both medical and recreational purposes. Although men are more likely to endorse past month cannabis use and are more frequently diagnosed with Cannabis Use Disorder relative to women, a growing proportion of medical cannabis users are reported to be women. The increased popularity of cannabis for medical purposes and the narrowing gap in prevalence of use between men and women raises questions regarding sex-dependent effects related to therapeutic efficacy and negative health effects of cannabis and cannabinoids. The objective of this review is to provide a translational perspective on the sex-dependent effects of cannabis and cannabinoids by synthesizing findings from preclinical and clinical studies focused on sex comparisons of their therapeutic potential and abuse liability, two specific areas that are of significant public health relevance. Hormonal and pharmacological mechanisms that may underlie sex differences in the effects of cannabis and cannabinoids are highlighted

Considering abuse liability and neurocognitive effects of cannabis and cannabis-derived products when assessing analgesic efficacy: a comprehensive review of randomized-controlled studies

Background: Pain is the most frequent indication for which medical cannabis treatment is sought.Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics

Changes in medical and non-medical cannabis use among United States adults before and during the COVID-19 pandemic

Background: During the SARS-CoV-2 pandemic, cannabis dispensaries in the United States (US) reported increased sales.Objectives: This study assessed changes in cannabis use before to during the pandemic; it was hypothesized that cannabis use increased during the pandemic.Methods: A US-based survey of adults assessed patterns of use before and during the pandemic. Participants recruited via social media from 8/2020 to 9/2020 self-reported medical and non-medical cannabis use. Use was categorized as ≤ monthly, weekly, and daily/almost daily; adjusted logistic regressions determined associations between cannabis use before the pandemic with change in frequency during the pandemic.Results: Of 1,886 respondents (63% male),1,113 reported non-medical and 603 medical use of cannabis. Those reporting ≤monthly non-medical use before the pandemic had higher odds of increasing use during the pandemic than those using weekly before the pandemic (AOR 3.2 [95% CI 2.2-4.5]). Those reporting ≤ monthly and daily medical cannabis use before the pandemic had higher odds of increasing use during the pandemic than those using weekly before the pandemic (AOR 2.3 [95% 1.3, 3.9]; AOR 2.4 [95% CI 1.2, 5.1] respectively).Conclusions: The most notable increases in cannabis use during the pandemic were among those who reported using cannabis least frequently before the pandemic (two to three times odds of increased use among ≤ monthly use compared to weekly). These findings have important implications for potential health consequences related to increased cannabis use both during and after the pandemic, even in populations thought to be protected by minimal use prior to the pandemic

Drugs of Misuse: Focus on Vascular Dysfunction

Common drugs of misuse, including cannabis, opioids, stimulants, alcohol, and anabolic steroids, have strikingly disparate acute and chronic vascular effects, leading to a wide range of clinical cardiovascular presentations. Acute cannabis smoking has been associated with increased risk for myocardial infarction and ischemic stroke in otherwise healthy young people. However, it remains uncertain if people who exclusively smoke cannabis have increased risk for accelerated atherosclerosis similar to that found in people who exclusively smoke tobacco cigarettes. Cocaine and methamphetamines, both stimulants, increase risk for stroke, myocardial infarction, aortic dissection, and accelerated atherosclerosis, but only methamphetamine use is strongly linked to pulmonary hypertension. Chronic alcohol use is strongly associated with chronic hypertension and hemorrhagic stroke, but perhaps confers a lower risk for myocardial infarction. Finally, anabolic steroid use, presumably through adverse effects on circulating lipids and the hematopoietic system, is associated with increased risk for accelerated atherosclerosis and myocardial infarction. Physicians, especially cardiologists, emergency medicine, and internal medicine physicians, should be familiar with the short- and long-term vascular consequences of use of these substances, thereby ensuring appropriate, specific, and informed counselling and treatment