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Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC)

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Abstract

Background

Cannabis is the most common illicit drug used in the USA and its use has been rising over the past decade, while the historical gap in rates of use between men and women has been decreasing. Sex differences in the effects of cannabinoids have been reported in animal models, but human studies are sparse and inconsistent. We investigated the sex differences in the acute subjective, psychotomimetic, cognitive, and physiological effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis.

Methods

Healthy male and female individuals, with limited exposure to cannabis, participated in a double blind, placebo-controlled study of intravenous (IV) placebo or THC at two doses (0.015 mg/kg and 0.03 mg/kg). Visual analog scale (VAS) was used to measure subjective effects, Psychotomimetic States Inventory (PSI) and the Clinician-Administered Dissociative Symptoms Scale (CADSS) were used to assess the psychotomimetic effects and perceptual alterations, respectively, and Rey Auditory Verbal Learning Task (RAVLT) was used to evaluate cognitive effects. Outcome variables were represented as the peak change from baseline for each variable, except RAVLT which was used only once per the test day after the subjective effects.

Results

A total of 42 individuals participated in this study. There were no significant differences between male and female participants in background characteristics. There was a significant main effect of sex on the VAS scores for THC-induced “High” (F1,38 = 4.27, p < 0.05) and a significant dose × sex interaction (F2,77 = 3.38, p < 0.05) with female participants having greater “High” scores than male participants at the lower THC dose (0.015 mg/kg). No other sex differences were observed in acute subjective, psychotomimetic, cognitive, or physiological effects of THC.

Conclusion

There were significant sex differences in subjective effects of feeling “High” at a lower dose of THC. However, there were no other sex-related differences in the subjective, physiological, or cognitive effects of THC.

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Funding

Anahita Bassir Nia was supported by the National Institute of Health K12 DA000167 grant.

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Authors and Affiliations

  1. Schizophrenia Neuropharmacology Research Group, VA Connecticut Healthcare System, West Haven, CT, USA

    Anahita Bassir Nia, Leigh Flynn, Christina Luddy, Deepak Cyril D’Souza, Patrick D. Skosnik, Brian Pittman & Mohini Ranganathan

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Anahita Bassir Nia, Maria J. Orejarena, Deepak Cyril D’Souza, Patrick D. Skosnik & Mohini Ranganathan

  3. The Clinical Neuroscience Research Unit (CNRU), Connecticut Mental Health Center (CMHC), Room 333B, 34 Park St, New Haven, CT, 06519, USA

    Anahita Bassir Nia

  4. Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Science Center, Houston, TX, USA

    Maria J. Orejarena

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  1. Anahita Bassir Nia
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  2. Maria J. Orejarena
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  3. Leigh Flynn
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  8. Mohini Ranganathan
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Correspondence to Anahita Bassir Nia.

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Conflict of interest

Anahita Bassir Nia is a member of Scientific Advisory Committee of Synendos Therapeutics AG, Switzerland. Authors have no other conflict of interest to disclose.

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Anahita Bassir Nia and Maria J. Orejarena are both first authors.

This article belongs to a Special Issue on Cannabis and Cannabinoids

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Bassir Nia, A., Orejarena, M.J., Flynn, L. et al. Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC). Psychopharmacology 239, 1621–1628 (2022). https://doi.org/10.1007/s00213-022-06135-3

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