PMID- 38377580
OWN - NLM
STAT- MEDLINE
DCOM- 20240405
LR  - 20240405
IS  - 2378-8763 (Electronic)
IS  - 2378-8763 (Linking)
VI  - 9
IP  - 2
DP  - 2024 Apr
TI  - Tolerability of High-Dose Oral Delta(9)-THC: Implications for Human Laboratory Study 
      Design.
PG  - 437-448
LID - 10.1089/can.2023.0209 [doi]
AB  - Background: Delta(9)-tetrahydrocannabinol (THC), the primary intoxicating compound in 
      cannabis, has been tested extensively in controlled administration human studies. 
      Some studies require a high THC dose that may induce adverse events (AEs), such 
      as those testing novel treatments for cannabinoid overdose. Although there are 
      ethical concerns related to administering high THC doses, there is no systematic 
      analysis on studies utilizing these doses. In this review, we examine studies 
      that administered oral THC doses >/=30 mg ("high-dose THC"), focusing on reported 
      tolerability, subjective effects, and pharmacokinetics (PK), with the objective 
      to inform the design of future studies. Methods: A comprehensive PubMed search 
      was performed to identify studies meeting pre-specified criteria. Results: Our 
      search identified 27 publications from 17 high-dose oral THC laboratory studies, 
      with single doses up to 90 mg and multiple doses up to 210 mg per day. The 
      maximum plasma THC concentration (C(max)) appeared to increase in a 
      dose-proportional manner over this dose range. All high-dose THC studies enrolled 
      participants with previous cannabis experience, although current use ranged from 
      nonusers to regular cannabis users. High-dose THC was generally well tolerated 
      with transient mild to moderate AE, including nausea and vomiting, anxiety, 
      paranoia, and sedation. There were occasional participant withdrawals due to AEs, 
      but there were no serious AE. Participants with frequent cannabis use tolerated 
      high-dose THC best. Conclusion: Although based on limited data, THC was generally 
      adequately tolerated with single oral doses of at least 50 mg in a controlled 
      laboratory setting in healthy participants with past cannabis experience.
FAU - Rozanc, Jan
AU  - Rozanc J
AUID- ORCID: 0000-0003-4283-6087
AD  - Verdient Science LLC, Denver, Colorado, USA.
AD  - Institute of Biomedical Sciences, Faculty of Medicine, University of Maribor, 
      Maribor, Slovenia.
FAU - Klumpers, Linda E
AU  - Klumpers LE
AUID- ORCID: 0000-0003-3453-9744
AD  - Verdient Science LLC, Denver, Colorado, USA.
AD  - Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
FAU - Huestis, Marilyn A
AU  - Huestis MA
AUID- ORCID: 0000-0003-2137-4645
AD  - Institute of Emerging Health Professions, Thomas Jefferson University, 
      Philadelphia, Pennsylvania, USA.
FAU - Tagen, Michael
AU  - Tagen M
AD  - Verdient Science LLC, Denver, Colorado, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20240219
PL  - United States
TA  - Cannabis Cannabinoid Res
JT  - Cannabis and cannabinoid research
JID - 101684827
RN  - 7J8897W37S (Dronabinol)
RN  - 0 (Cannabinoids)
SB  - IM
MH  - Humans
MH  - Dronabinol/adverse effects
MH  - *Cannabis
MH  - *Cannabinoids/adverse effects
MH  - Research Design
MH  - Anxiety
OTO - NOTNLM
OT  - adverse events
OT  - pharmacokinetics
OT  - tolerability
OT  - Delta9-tetrahydrocannabinol
EDAT- 2024/02/20 18:42
MHDA- 2024/04/05 06:44
CRDT- 2024/02/20 17:25
PHST- 2024/04/05 06:44 [medline]
PHST- 2024/02/20 18:42 [pubmed]
PHST- 2024/02/20 17:25 [entrez]
AID - 10.1089/can.2023.0209 [doi]
PST - ppublish
SO  - Cannabis Cannabinoid Res. 2024 Apr;9(2):437-448. doi: 10.1089/can.2023.0209. Epub 
      2024 Feb 19.