Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism.
Mohini Ranganathan, R Andrew Sewell, Michelle Carbuto, Jacqueline Elander, Ashley Schnakenberg, Rajiv Radhakrishnan, Brian Pittman, Deepak Cyril D'Souza
Psychopharmacology June 2014 DOI: 10.1007/s00213-013-3402-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled crossover trial Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy volunteers |
| Dose | 0.018 and 0.036 mg/kg intravenously |
| Duration | Three test days |
| Measures | subjective high, perceptual alterations, memory impairment, stimulatory and depressant subjective effects, attention, spatial memory, executive function, THC blood levels, 11-hydroxy-THC blood levels |
| Topics | Cannabis |
| Key findings | Greater family history of alcoholism correlated with greater subjective "high" and perceptual alterations induced by Δ(9)-THC, suggesting that altered CB1R function may contribute to vulnerability to alcohol misuse. |
Abstract
A family history (FH) of alcoholism accounts for approximately 50% of the risk of developing alcohol problems. Several lines of preclinical evidence suggest that brain cannabinoid receptor (CB1R) function may mediate the effects of alcohol and risk for developing alcoholism including the observations that reduced CB1R function decreases alcohol-related behaviors and enhanced CB1R function increases them. In this first human study, we probed CB1R function in individuals vulnerable to alcoholism with the exogenous cannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Healthy volunteers (n = 30) participated in a three test day study during which they received 0.018 and 0.036 mg/kg of Δ(9)-THC, or placebo intravenously in a randomized, counterbalanced order under double-blind conditions. Primary outcome measures were subjective "high," perceptual alterations, and memory impairment. Secondary outcome measures consisted of stimulatory and depressant subjective effects, attention, spatial memory, executive function, Δ(9)-THC and 11-hydroxy-THC blood levels, and other subjective effects. FH was calculated using the Family Pattern Density method and was used as a continuous variable. Greater FH was correlated with greater "high" and perceptual alterations induced by Δ(9)-THC. This enhanced sensitivity with increasing FH was specific to Δ(9)-THC's rewarding effects and persisted even when FH was calculated using an alternate method. Enhanced sensitivity to the rewarding effects of Δ(9)-THC in high-FH volunteers suggests that alterations in CB1R function might contribute to alcohol misuse vulnerability.