Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol.
Joshua A Lile, Thomas H Kelly, David J Pinsky, Lon R Hays
Psychopharmacology April 2009 DOI: 10.1007/s00213-008-1393-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Double-blind Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Healthy subjects who reported moderate cannabis use |
| Interventions | Delta(9)-tetrahydrocannabinol Triazolam Hydromorphone Methylphenidate |
| Dose | 25 mg Delta(9)-THC training dose; multiple doses of test drugs |
| Topics | Cannabis |
| Key findings | Only Delta(9)-THC substituted for the training dose; triazolam, hydromorphone, and methylphenidate did not. This suggests that THC's discriminative-stimulus effects are not directly mediated by opioid, GABA, or dopamine systems. |
Abstract
Preclinical evidence suggests that non-cannabinoid neurotransmitter systems are involved in the behavioral and physiological effects of cannabinoids, but relatively little research has been conducted in humans. The aims of this study were to assess whether oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC) would function as a discriminative stimulus in humans and to examine the substitution profile of drugs acting at opioid, GABA, and dopamine systems. Healthy subjects who reported moderate cannabis use were enrolled. Subjects learned to identify when they received oral 25 mg Delta(9)-THC or placebo under double-blind conditions. Once subjects acquired the discrimination (i.e., > or =80% drug-appropriate responding for four consecutive sessions), multiple doses of Delta(9)-THC, the GABA(A) positive modulator triazolam, the micro-opioid agonist hydromorphone and the dopamine reuptake inhibitor methylphenidate were tested to determine if they shared discriminative-stimulus effects with the training dose of Delta(9)-THC. Eight subjects (N = 8) accurately discriminated Delta(9)-THC and completed the study. The training dose of Delta(9)-THC functioned as a discriminative stimulus and produced prototypical subject-rated drug effects. All of the drugs tested produced significant effects on the self-report questionnaires, but only Delta(9)-THC substituted for the training dose. These results suggest that the discriminative-stimulus effects of Delta(9)-THC in humans are not directly mediated through central neurotransmitter systems acted upon by the drugs tested in this study.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cited by 16
- Finding order in chemical chaos - Continuing characterization of synthetic cannabinoid receptor agonists. Neuropharmacology May 15, 2018
- Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs. Current Topics in Behavioral Neurosciences 2018
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
- Sex differences in the subjective effects of oral Δ9-THC in cannabis users. Pharmacology, Biochemistry, and Behavior January 2017
- Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug and Alcohol Dependence October 1, 2014
and 11 more in the library
Cites 9
- Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology November 2007
- Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers. Neuropsychopharmacology June 2007
- The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers. American heart journal March 2006
- Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology June 2005
- Delta(9)-THC-induced cognitive deficits in mice are reversed by the GABA(A) antagonist bicuculline. Psychopharmacology March 2005
and 4 more in the library