Rationale Stimulant drugs such as methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) can impact neurobiological systems implicated in stress, reward processing, and drug use. Although recent preclinical evidence implicates the endocannabinoid (eCB) system in these processes, little is known about the acute effects of stimulants on eCB levels in humans. Objectives The aim of the present study was to investigate the effects of acute administration of the prototypical psychostimulant MA and the psychostimulant-empathogen MDMA on circulating eCB levels in healthy adults. Methods Using a within-subject, double-blind design, this study assessed the acute effects of MA (20 mg), MDMA (100 mg), and placebo on plasma eCB levels in healthy human participants (N = 22) during three separate sessions. Blood samples assessing concentrations of the eCBs anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) were collected between 150- and 180-minutes post-drug administration, and subjective measures of drug effects were collected at regular intervals. Results MA, but not MDMA, was associated with significantly lower 2-AG plasma concentrations compared to placebo. Neither drug impacted AEA concentrations. However, during the placebo condition, higher AEA concentrations were correlated with disliking the ‘drug effects’, suggesting a possible relationship between AEA levels and negative expectations of subjective drug effects. Conclusions These findings provide novel insights into how stimulant drugs act on the eCB system and may help to develop treatments for SUDs.

Interactions between metabolic interoception and regulation may drive comorbidity between mental and metabolic ill-health.

Rationale Harmful alcohol use remains a significant global public health challenge. Examining variability in the acute subjective effects of alcohol and related neurobiological mechanisms may advance the understanding of susceptibility to harmful alcohol use. Research suggests the endocannabinoid (eCB) system may play an important role in mediating the reinforcing effects of alcohol. This study examined the relationship between alcohol-induced changes in eCB concentrations and the subjective psychoactive effects of acute alcohol consumption. Method Healthy social drinkers (n = 28, aged 20–35 years) participated in a within-subjects, single-blind, placebo-controlled laboratory alcohol challenge study. Alcohol (0.6 g/kg; with 20% adjustment for women) and placebo sessions were counterbalanced. Subjective alcohol effects were assessed from self-report questionnaires administered pre- and post-dosing, including the Biphasic Alcohol Effects Scale (BAES), Drug Effects Questionnaire (DEQ), and Profile of Mood States (POMS). The eCBs, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma taken throughout the dosing session. Results Acute alcohol was associated with an overall decrease in 2-AG concentrations compared to placebo. Further, we found that a drop in 2-AG concentrations was associated with less drug ‘liking’ and feelings of ‘friendliness’, whereas under placebo conditions, a rise in 2-AG was associated with a smaller decrease in feelings of ‘stimulation’ (e.g., feeling energized, talkative). Alcohol did not significantly affect AEA concentrations. Conclusion Our study provides the first evidence that eCBs may contribute to individual differences in sensitivity to alcohol's reward-related mechanisms by influencing subjective experience, offering insight into the potential role of eCBs in the processes underlying harmful alcohol use.

The portrayal of uncaring scientists without any thought for the animals being used in their research is far from the truth.

A policy of ending pediatric COVID vaccination will disable, hospitalize and even kill Albertan children, leaving blood on Smith’s hands.

Rationale Low socioeconomic status people make up a majority of those who use cannabis during pregnancy. Both developmental cannabis exposure and developmental stress increase the risk of developing p...

Today, the Canadian Medical Association (CMA), along with three Alberta doctors, will file a constitutional challenge to Alberta’s Bill 26, to protect the relationship between patients, their families...

Objective Decades of research have identified a strong association between heavy cannabis use and schizophrenia, with evidence of correlated genetic factors. However, many studies on the genetic relat...