Intercannabinoid and cannabinoid-ethanol interactions and their effects on human performance

Bird, Kevin D.; Boleyn, T.; Chesher, G. B.; Jackson, David M.; Starmer, G. A.; Teo, R. K. C.

doi:10.1007/bf00434409

Cited by 46 publications

(51 citation statements)

References 24 publications

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“…Both THC and ethanol produced significant performance decrements and their combined effects were described in terms of an additive model. There was no suggestion of any effects produced by CBD or CBN in the doses used nor was there any evidence that these substances modified the effects of either THC or ethanol (Bird et al, 1980).…”

Section: Ethanol and Drugsmentioning

confidence: 76%

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Investigating drug‐ethanol interactions.

Starmer¹,

Bird²

1984

Brit J Clinical Pharma

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Methodology developed in our laboratories for testing the interactive effects of ethanol and drugs on human psychomotor performance is discussed. An attempt has been made to relate the findings of our studies to the results of real‐life impairment, particularly in traffic crashes. Proposals for more comprehensive testing of drug‐ethanol interactions have been put forward which may increase the predictive value of such tests.

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Section: Ethanol and Drugsmentioning

confidence: 76%

“…Bird et al, 1980;MacPherson et al, 1984), where preparations are suggested to ameliorate the inebriant effects of ethanol or to make comparisons among drugs which are used for essentially the same therapeutic purposes (Franks et al, 1978(Franks et al, , 1981.…”

Section: Discussionmentioning

confidence: 99%

Investigating drug‐ethanol interactions.

Starmer¹,

Bird²

1984

Brit J Clinical Pharma

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“…Also, given that acute cannabis produces detrimental effects on psychomotor performance, and that these effects are generally additive with those of alcohol (Manno et al 1971;Chesher et al 1976Chesher et al , 1977Belgrave et al 1979;Bird et al 1980;Starmer and Bird 1984;Chait and Perry 1994), it seems unlikely that residual cannabinoids in plasma could exert oppositional effects pharmacodynamically. In fact, there is little evidence for detectable effects of cannabis on related tasks extending beyond about 7 h from last use (Hansteen et al 1976; Barnett et al 1985;Chait et al 1985;Cone et al 1986;Gieringer 1988;Heishman et al 1989;Chait 1990;Chait and Pierri 1992;Chait and Perry 1994), although there have been isolated reports of deleterious effects on aircraft simulator performance 24 h after last use (Yesavage et al 1985;Leirer et al 1991).…”

Section: Discussionmentioning

confidence: 96%

“…The performance effects of alcohol and cannabis are frequently reported to be similar in several respects, although qualitative differences between the effects of the two drugs have also been identified (Bech et al 1973;Rafaelson et al 1973aRafaelson et al , 1973bHansteen et al 1976;Belgrave et al 1979;Bird et al 1980;Chait and Perry 1994;Heishman et al 1997;Robbe 1998). In acute combination, alcohol and cannabis tend to produce additive effects (Manno et al 1971;Chesher et al 1976Chesher et al , 1977Belgrave et al 1979;Bird et al 1980;Starmer and Bird 1984;Chait and Perry 1994).…”

Section: Introductionmentioning

confidence: 90%

“…In acute combination, alcohol and cannabis tend to produce additive effects (Manno et al 1971;Chesher et al 1976Chesher et al , 1977Belgrave et al 1979;Bird et al 1980;Starmer and Bird 1984;Chait and Perry 1994). Less common are reports of synergistic effects following conjoint administration (MacAvoy and Marks 1975;Sutton 1983;Perez-Reyez et al 1988;Robbe 1998).…”

Section: Introductionmentioning

confidence: 91%

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Modulation of the effects of alcohol on driving-related psychomotor skills by chronic exposure to cannabis

Wright

Terry

2002

Psychopharmacology

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For psychomotor skills relevant to driving, chronic cannabis use (in the absence of acute administration) does not potentiate the effects of alcohol. In fact, the superior tracking accuracy of regular users relative to infrequent users after alcohol, and their lower scores for dizziness, suggest that chronic cannabis use may instead confer cross-tolerance to specific effects of alcohol on behaviour.

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Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial

et al. 2023

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ImportanceControlled clinical laboratory studies have shown that cannabidiol (CBD) can sometimes attenuate or exacerbate the effects of Δ9-tetrahydrocannabinol (Δ9-THC). No studies have evaluated differences in pharmacokinetics (PK) of Δ9-THC and pharmacodynamics (PD) between orally administered cannabis extracts that vary with respect to Δ9-THC and CBD concentrations.ObjectiveTo compare the PK and PD of orally administered Δ9-THC-dominant and CBD-dominant cannabis extracts that contained the same Δ9-THC dose (20 mg).Design, Setting, and ParticipantsThis randomized clinical trial was a within-participant, double-blind, crossover study conducted from January 2021 to March 2022 at the Johns Hopkins University Behavioral Pharmacology Research Unit, Baltimore, MD. Eighteen healthy adults completed 3 randomized outpatient experimental test sessions that were each separated by at least 1 week.InterventionsBrownies containing (1) no cannabis extract (ie, placebo); (2) Δ9-THC-dominant extract (20 mg Δ9-THC with no CBD); and (3) CBD-dominant extract (20 mg Δ9-THC + 640 mg CBD) were administered to participants 30 minutes prior to administering a cytochrome P450 (CYP) probe drug cocktail, which consisted of 100 mg caffeine, 20 mg omeprazole, 25 mg losartan, 30 mg dextromethorphan, and 2 mg midazolam.Main Outcomes and MeasuresChange-from-baseline plasma concentrations for Δ9-THC or Δ9-THC metabolites and scores for subjective drug effects, cognitive and psychomotor performance, and vital signs. The area under the plasma vs concentration vs time curve (AUC) and maximum plasma concentration (Cmax) were determined.ResultsThe participant cohort of 18 adults included 11 males (61.1%) and 7 females (38.9%) with a mean (SD) age of 30 (7) years who had not used cannabis for at least 30 days prior to initiation of the study (mean [SD] day since last cannabis use, 86 [66] days). The CYP cocktail + placebo brownie and the CYP cocktail did not affect any PD assessments. Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH. The CYP cocktail + Δ9-THC + CBD increased self-reported anxiety, sedation, and memory difficulty, increased heart rate, and produced a more pronounced impairment of cognitive and psychomotor performance compared with both CYP cocktail + Δ9-THC and CYP cocktail + placebo.Conclusions and RelevanceIn this randomized clinical trial of oral Δ9-THC and CBD, stronger adverse effects were elicited from a CBD-dominant cannabis extract compared with a Δ9-THC-dominant cannabis extract at the same Δ9-THC dose, which contradicts common claims that CBD attenuates the adverse effects of Δ9-THC. CBD inhibition of Δ9-THC and 11-OH-Δ9-THC metabolism is the likely mechanism for the differences observed. An improved understanding of cannabinoid-cannabinoid and cannabinoid-drug interactions are needed to inform clinical and regulatory decision-making regarding the therapeutic and nontherapeutic use of cannabis products.Trial Registrationclinicaltrials.gov Identifier: NCT04201197

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Intercannabinoid and cannabinoid-ethanol interactions and their effects on human performance

Cited by 46 publications

References 24 publications

Investigating drug‐ethanol interactions.

Investigating drug‐ethanol interactions.

Modulation of the effects of alcohol on driving-related psychomotor skills by chronic exposure to cannabis

Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial

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