Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis

Background: While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC). Methods: Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC. Results: There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo. Conclusions: Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.

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Association between aggressiveness, schizotypal personality traits and cannabis use in Swiss psychology students

Psychiatry Research ◽

10.1016/j.psychres.2005.07.034 ◽

2006 ◽

Vol 143 (2-3) ◽

pp. 299-301 ◽

Cited By ~ 6

Author(s):

Michael Schaub ◽

Lukas Boesch ◽

Rudolf Stohler

Keyword(s):

Personality Traits ◽

Psychology Students ◽

Cannabis Use ◽

Schizotypal Personality

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Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.077503 ◽

2010 ◽

Vol 197 (4) ◽

pp. 285-290 ◽

Cited By ~ 178

Author(s):

Celia J. A. Morgan ◽

Gráinne Schafer ◽

Tom P. Freeman ◽

H. Valerie Curran

Keyword(s):

Harm Reduction ◽

Memory Impairment ◽

Naturalistic Study ◽

Acute Effects ◽

Antagonistic Effects ◽

Opposing Effects ◽

Prose Recall ◽

Psychotomimetic Effects ◽

Drug Free

BackgroundThe two main constituents of cannabis, cannabidiol and δ9-tetrahydrocannabinol (THC), have opposing effects both pharmacologically and behaviourally when administered in the laboratory. Street cannabis is known to contain varying levels of each cannabinoid.AimsTo study how the varying levels of cannabidiol and THC have an impact on the acute effects of the drug in naturalistic settings.MethodCannabis users (n = 134) were tested 7 days apart on measures of memory and psychotomimetic symptoms, once while they were drug free and once while acutely intoxicated by their own chosen smoked cannabis. Using an unprecedented methodology, a sample of cannabis (as well as saliva) was collected from each user and analysed for levels of cannabinoids. On the basis of highest and lowest cannabidiol content of cannabis, two groups of individuals were directly compared.ResultsGroups did not differ in the THC content of the cannabis they smoked. Unlike the marked impairment in prose recall of individuals who smoked cannabis low in cannabidiol, participants smoking cannabis high in cannabidiol showed no memory impairment. Cannabidiol content did not affect psychotomimetic symptoms, which were elevated in both groups when intoxicated.ConclusionsThe antagonistic effects of cannabidiol at the CB1 receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC. In terms of harm reduction, users should be made aware of the higher risk of memory impairment associated with smoking low-cannabidiol strains of cannabis like ‘skunk’ and encouraged to use strains containing higher levels of cannabidiol.

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Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

Psychological Medicine ◽

10.1017/s0033291720003827 ◽

2020 ◽

pp. 1-8

Author(s):

Marco Colizzi ◽

Nathalie Weltens ◽

David J Lythgoe ◽

Steve CR Williams ◽

Lukas Van Oudenhove ◽

...

Keyword(s):

Hpa Axis ◽

Surrogate Marker ◽

Anterior Cingulate ◽

Differential Sensitivity ◽

Acute Effects ◽

Double Blind ◽

Glial Function ◽

Cortisol Levels ◽

Psychotomimetic Effects ◽

Hpa Axis Activity

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.

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Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis

Molecular Psychiatry ◽

10.1038/s41380-019-0374-8 ◽

2019 ◽

Vol 25 (12) ◽

pp. 3231-3240 ◽

Cited By ~ 20

Author(s):

Marco Colizzi ◽

Nathalie Weltens ◽

Philip McGuire ◽

David Lythgoe ◽

Steve Williams ◽

...

Keyword(s):

Cannabis Use ◽

Striatal Dopamine ◽

Resonance Spectroscopy ◽

Acute Administration ◽

Double Blind ◽

Glutamate Signaling ◽

Caudate Head ◽

Lower Baseline ◽

Left Caudate ◽

Psychotomimetic Effects

AbstractThe neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.

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Cannabis use correlates with schizotypal personality traits in healthy students

Psychiatry Research ◽

10.1016/s0165-1781(01)00358-4 ◽

2002 ◽

Vol 109 (1) ◽

pp. 27-35 ◽

Cited By ~ 61

Author(s):

Patrick Dumas ◽

Mohamed Saoud ◽

Sébastien Bouafia ◽

Christel Gutknecht ◽

René Ecochard ◽

...

Keyword(s):

Personality Traits ◽

Cannabis Use ◽

Schizotypal Personality

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The Acute Effects of Androstenedione Supplementation in Healthy Young Males

Canadian Journal of Applied Physiology ◽

10.1139/h00-005 ◽

2000 ◽

Vol 25 (1) ◽

pp. 68-78 ◽

Cited By ~ 34

Author(s):

Craig S. Ballantyne ◽

Stuart M. Phillips ◽

Jay R. Macdonald ◽

Mark A. Tarnopolsky ◽

J. Duncan Macdougall

Keyword(s):

Luteinizing Hormone ◽

Resistance Exercise ◽

Elevated Plasma ◽

Acute Effects ◽

Double Blind ◽

Male Athletes ◽

Young Males ◽

Plasma Estradiol ◽

Key Words Testosterone ◽

Heavy Resistance Exercise

We examined the effects of androstenedione supplementation on the hormonal profile of 10 males and its interaction with resistance exercise. Baseline testosterone, luteinizing hormone, estradiol, and androstenedione concentrations were established by venous sampling at 3 hr intervals over 24 hr. Subjects ingested 200 mg of androstenedione daily for 2 days, with second and third day blood samples. Two weeks later, they ingested androstenedione or a placebo for 2 days, in a double-blind, cross-over design. On day 2, they performed heavy resistance exercise with blood sampled before, after, and 90 min post. The supplement elevated plasma androstenedione 2-3-fold and luteinizing hormone ∼70% but did not alter testosterone concentration. Exercise elevated testosterone, with no difference between conditions. Exercise in the supplemented condition significantly elevated plasma estradiol by ∼83% for 90 min. Androstenedione supplementation, thus, is unlikely to provide male athletes with any anabolic benefit and, with heavy resistance exercise, elevates estrogen. Key Words: testosterone, luteinizing hormone, estradiol, fluid shifts, resistance exercise

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