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Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism.
Psychopharmacology (Berl). 2014 Jun; 231(12):2385-93.P

Abstract

BACKGROUND AND AIMS

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).

DESIGN, SETTING, AND PARTICIPANTS

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.

MEASUREMENTS

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.

FINDINGS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Schizophrenia and Neuropharmacology Research Group, VA Connecticut Healthcare System, West Haven, CT, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24424782

Citation

Ranganathan, Mohini, et al. "Effects of Δ9-tetrahydrocannabinol in Individuals With a Familial Vulnerability to Alcoholism." Psychopharmacology, vol. 231, no. 12, 2014, pp. 2385-93.
Ranganathan M, Sewell RA, Carbuto M, et al. Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism. Psychopharmacology (Berl). 2014;231(12):2385-93.
Ranganathan, M., Sewell, R. A., Carbuto, M., Elander, J., Schnakenberg, A., Radhakrishnan, R., Pittman, B., & D'Souza, D. C. (2014). Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism. Psychopharmacology, 231(12), 2385-93. https://doi.org/10.1007/s00213-013-3402-4
Ranganathan M, et al. Effects of Δ9-tetrahydrocannabinol in Individuals With a Familial Vulnerability to Alcoholism. Psychopharmacology (Berl). 2014;231(12):2385-93. PubMed PMID: 24424782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism. AU - Ranganathan,Mohini, AU - Sewell,R Andrew, AU - Carbuto,Michelle, AU - Elander,Jacqueline, AU - Schnakenberg,Ashley, AU - Radhakrishnan,Rajiv, AU - Pittman,Brian, AU - D'Souza,Deepak Cyril, Y1 - 2014/01/15/ PY - 2013/10/24/received PY - 2013/12/02/accepted PY - 2014/1/16/entrez PY - 2014/1/16/pubmed PY - 2015/1/16/medline SP - 2385 EP - 93 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 231 IS - 12 N2 - BACKGROUND AND AIMS: 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). DESIGN, SETTING, AND PARTICIPANTS: 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. MEASUREMENTS: 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. FINDINGS: 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. CONCLUSIONS: 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/24424782/Effects_of_Δ9_tetrahydrocannabinol_in_individuals_with_a_familial_vulnerability_to_alcoholism_ L2 - https://dx.doi.org/10.1007/s00213-013-3402-4 DB - PRIME DP - Unbound Medicine ER -