Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis.
Deepak Cyril D'Souza, Mohini Ranganathan, Gabriel Braley, Ralitza Gueorguieva, Zoran Zimolo, Thomas B. Cooper, Edward Perry, John H. Krystal
Neuropsychopharmacology September 2008 DOI: 10.1038/sj.npp.1301643 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 52 |
| Population | Frequent cannabis users and healthy controls |
| Intervention | Delta-9-THC |
| Dose | 0, 2.5, and 5 mg intravenous |
| Duration | 3-day study |
| Topics | Cannabis |
| Key findings | Frequent cannabis users showed blunted psychotomimetic, perceptual, cognitive, anxiogenic, and cortisol responses to intravenous Delta-9-THC compared with controls, but similar euphoric effects, suggesting tolerance or inherent blunting. |
Abstract
Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Delta-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Delta-9-THC has not been established. In a 3-day, double-blind, randomized, placebo-controlled study, the dose-related effects of 0, 2.5, and 5 mg intravenous Delta-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls. Delta-9-THC (1) produced transient psychotomimetic effects and perceptual alterations; (2) impaired memory and attention; (3) increased subjective effects of 'high'; (4) produced tachycardia; and (5) increased serum cortisol in both groups. However, relative to controls, frequent users showed blunted responses to the psychotomimetic, perceptual altering, cognitive impairing, anxiogenic, and cortisol increasing effects of Delta-9-THC but not to its euphoric effects. Frequent users also had lower prolactin levels. These data suggest that frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 75
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users Psychopharmacology October 30, 2010
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
and 70 more in the library
Cites 11
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Cannabis use and psychotic disorders: an update Drug and Alcohol Review November 30, 2004
- Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophrenia Research August 2007
- The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology August 2004
- Cannabis use and risk of psychosis: an etiological link? Epidemiologia e Psichiatria Sociale June 1, 2004
and 6 more in the library