Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol
Marco Colizzi, Nathalie Weltens, David J Lythgoe, Steven C. R. Williams, Lukas Van Oudenhove, Sagnik Bhattacharyya
Psychological Medicine October 27, 2020 DOI: 10.1017/s0033291720003827 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy participants (seven males) with modest previous cannabis exposure |
| Intervention | Delta-9-tetrahydrocannabinol (Δ9-THC) |
| Dose | 1.19 mg/2 ml |
| Topics | Cannabis |
| Citations | 8 |
| Key points | Participants sensitive to the psychotomimetic effects of delta-9-THC showed a decrease in anterior cingulate cortex myo-inositol and a disruption of the physiological diurnal cortisol decline, whereas non-sensitive participants did not. The authors conclude that interindividual differences in transient psychosis-like effects of THC result from its differential impact on glial function and stress response. |
Abstract
Abstract Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested.
Methods: A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure.
Results: The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo;M= −0.251,s.d.= 1.242) and those not sensitive (M= 1.615,s.d.= 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459,p= 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo;M= −275.4,s.d.= 207.519) and those not sensitive (M= 74.2,s.d.= 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068,p= 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms.
Conclusions: The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.
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
Cites 13
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- Association Between Continued Cannabis Use and Risk of Relapse in First-Episode Psychosis JAMA Psychiatry September 28, 2016
- Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects ofδ-9-THC Psychological Medicine March 5, 2018
- Is there sufficient evidence that cannabis use is a risk factor for psychosis? 2020
- Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity. European Neuropsychopharmacology December 1, 2019
and 8 more in the library