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The safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories

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Abstract

Rationale

Delta-9-tetrahydrocannabinol (THC) is one of the few cannabinoid receptor ligands that can be used to probe the cannabinoid system in humans. Despite increasing interest in the cannabinoid receptor system, use of intravenous THC as a research tool has been limited by concerns about its abuse liability and psychoactive effects.

Objectives

This study aims to evaluate the safety of all intravenous THC studies conducted at this center for the past 13 years.

Methods

Included were 11 studies with 266 subjects (14 schizophrenia patients and 252 healthy subjects, of whom 76 were frequent cannabis users), 351 active THC infusions, and 226 placebo infusions. Subjects were monitored for subjective and physical adverse events and followed up to 12 months beyond study participation.

Results

There was one serious and 70 minor adverse events in 9.7% of subjects and 7.4% of infusions, with 8.5% occurring after the end of the test day. Nausea and dizziness were the most frequent side effects. Adverse events were more likely to be associated with faster infusion rates (2–5 min) and higher doses (>2.1 mg/70 kg). Of 149 subjects on whom long-term follow-up data were gathered, 94% reported either no change or a reduction in their desire to use cannabis in the post-study period, 18% stated that their cannabis use decreased, and 3% stated that it increased in the post-study period.

Conclusions

With careful subject selection and screening, risk to subjects is relatively low. Safeguards are generally sufficient and effective, reducing both the duration and severity of adverse events.

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Acknowledgments

The authors wish to acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse, and (5) the Yale Center for Clinical Investigation. All experiments complied with the current laws of the USA. No author has any conflict of interest or financial arrangement relevant to this manuscript. D. Cyril D’Souza has full control of all primary data and will allow Psychopharmacology to review the data if requested.

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Authors and Affiliations

  1. Psychiatry Service, VA Connecticut Healthcare System, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA

    Michelle Carbuto, R. Andrew Sewell, Ashley Williams, Kim Forselius-Bielen, Gabriel Braley, Jacqueline Elander, Ashley Schnakenberg, Savita Bhakta, Edward Perry, Mohini Ranganathan & Deepak Cyril D’Souza

  2. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA

    Kim Forselius-Bielen, Brian Pittman, Edward Perry, Mohini Ranganathan & Deepak Cyril D’Souza

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

    Michelle Carbuto, R. Andrew Sewell, Ashley Williams, Kim Forselius-Bielen, Gabriel Braley, Jacqueline Elander, Brian Pittman, Ashley Schnakenberg, Savita Bhakta, Edward Perry, Mohini Ranganathan & Deepak Cyril D’Souza

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  1. Michelle Carbuto
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  2. R. Andrew Sewell
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  3. Ashley Williams
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Consortia

The Yale THC Study Group

Corresponding author

Correspondence to Deepak Cyril D’Souza.

Additional information

Michelle Carbuto and R. Andrew Sewell share first authorship.

The Yale THC Study Group includes (in alphabetical order): Walid Abi-Saab, Yola Ammerman, Rebecca Blais, Vanessa Bufis, Brenda Breault, Tom Cooper, Anne Doersch, Lia Donahue, Angelina Genovese, Ralitza Gueorguieva, John Krystal, Lisa MacDougall, Steven Madonick, Elizabeth O’Donnell, Stephen Oliver, Michelle San Pedro, Nagendra Singh, Michael Vendetti and Yu-te Wu.

Electronic supplementary material

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Supplementary Table 1

Descriptions of behavioral distress related to THC (DOC 35 kb)

Supplementary Table 2

Subjects who experienced increased desire for cannabis post-study (DOC 42 kb)

Supplemental Table 3

Subjects who felt their use of THC in the lab increased their use of cannabis post-study (DOC 76.0 kb)

Supplemental case histories

(DOC 51.0 kb)

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Carbuto, M., Sewell, R.A., Williams, A. et al. The safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories. Psychopharmacology 219, 885–896 (2012). https://doi.org/10.1007/s00213-011-2417-y

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