Frequent cannabis users show an attenuated response to the psychotomimetic, amnestic and endocrine effects of i.v. THC, but not to its euphoric effect.
Summary
RCT (n=52: 30 frequent users, 22 healthy controls), IV Δ9-THC 0/2.5/5 mg vs. placebo. THC induced dose-dependent psychotomimetic effects and memory impairments in both groups. Frequent users showed significantly attenuated responses to psychotomimetic, cognitive and anxiogenic THC effects (development of tolerance), but no attenuation of the euphoric effect. Finding demonstrates tolerance to psychotomimetic cannabis effects with frequent use, not their absence.
P
PopulationFrequent cannabis users (n=30) and healthy control subjects (n=22), total n=52
I
InterventionIntravenous delta-9-THC in 3 dosages (0, 2,5 and 5 mg), 3-day crossover protocol
C
ControlPlacebo (0 mg i.v. THC) as well as healthy control subjects without cannabis exposure
O
OutcomeFrequent users showed attenuated psychotomimetic, perception-altering, cognitive, anxiogenic and cortisol-increasing effects of THC compared to controls; euphoric effects remained unimpaired
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeMixed
Citations / year★★★★★
Authors
D'Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J.
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.