title: The safety of studies with intravenous Δ⁹-tetrahydrocannabinol in humans, with case histories.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Carbuto
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Sewell
authors.forename: Ashley
authors.initials: A
authors.lastname: Williams
authors.forename: Kim
authors.initials: K
authors.lastname: Forselius-Bielen
authors.forename: Gabriel
authors.initials: G
authors.lastname: Braley
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Elander
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Ashley
authors.initials: A
authors.lastname: Schnakenberg
authors.forename: Savita
authors.initials: S
authors.lastname: Bhakta
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000293:Adolescent; D000328:Adult; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology*; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology*; D008875:Middle Aged; D010259:Paranoid Disorders / Q000139:chemically induced / Q000523:psychology*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D055815:Young Adult
chemical_list: D013759:Dronabinol