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      Acute Effects of Smoked and Vaporized Cannabis in Healthy Adults Who Infrequently Use Cannabis : A Crossover Trial

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          Key Points

          Question

          How does smoked and vaporized cannabis acutely influence subjective drug effects, cognitive and psychomotor performance, and cardiovascular measures in healthy adults who infrequently use cannabis (>30 days since last use)?

          Findings

          In a crossover trial of 17 healthy adults, inhalation of smoked and vaporized cannabis containing 10 mg of Δ9-tetrahydrocannabinol (THC) produced discriminative drug effects and modest impairment of cognitive functioning, while inhalation of a 25-mg dose of THC was associated with pronounced drug effects, increased incidence of adverse effects, and significant impairment of cognitive and psychomotor ability. Vaporized cannabis produced greater pharmacodynamic effects and higher concentrations of THC in blood compared with equal doses of smoked cannabis.

          Meaning

          Significant, sometimes adverse, drug effects can occur at relatively low THC doses in infrequent cannabis users, and accordingly these data should be considered with regard to regulation of retail cannabis products and education for individuals initiating cannabis use.

          Abstract

          Importance

          Vaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns (>30 days since last use) are needed.

          Objective

          To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods.

          Design, Setting, and Participants

          This within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster.

          Interventions

          Cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant.

          Main Outcomes and Measures

          Change from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration.

          Results

          The sample included 17 healthy adults (mean [SD] age, 27.3 [5.7] years; 9 men and 8 women) with no cannabis use in the prior month (mean [SD] days since last cannabis use, 398 [437] days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean [SD] ratings on a 100-point visual analog scale, smoked: 46 [26]; vaporized: 69 [26]) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean [SD] ratings, smoked: 66 [29]; vaporized: 78 [24]), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average.

          Conclusions and Relevance

          Vaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure.

          Trial Registration

          ClinicalTrials.gov Identifier: NCT03676166.

          Abstract

          This crossover study evaluates the acute effects of smoked vs vaporized cannabis use, at multiple Δ9-tetrahydrocannabinol (THC) doses, among healthy adults who infrequently use cannabis.

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          Most cited references24

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          Timeline Follow-Back: A Technique for Assessing Self-Reported Alcohol Consumption

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            Marijuana use and use disorders in adults in the USA, 2002–14: analysis of annual cross-sectional surveys

            The study of marijuana use disorders is urgently needed because of increasing marijuana legalisation in multiple jurisdictions, the effect of marijuana use on future risk of psychiatric disorders, and deleterious effects of marijuana exposure. Thus, understanding trends of marijuana use and use disorders and examining factors that might drive these trends (eg, perceptions of harms from marijuana use) is essential.
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              Routes of administration for cannabis use – basic prevalence and related health outcomes: A scoping review and synthesis

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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                30 November 2018
                November 2018
                21 December 2018
                30 November 2018
                : 1
                : 7
                : e184841
                Affiliations
                [1 ]Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, Maryland
                [2 ]RTI International, Research Triangle Park, North Carolina
                [3 ]Division of Workplace Programs, Substance Abuse and Mental Health Services Administration, Rockville, Maryland
                Author notes
                Article Information
                Accepted for Publication: September 28, 2018.
                Published: November 30, 2018. doi:10.1001/jamanetworkopen.2018.4841
                Correction: This article was corrected on December 21, 2018, to fix a wording error in the title of the Table.
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2018 Spindle TR et al. JAMA Network Open .
                Corresponding Author: Ryan Vandrey, PhD, Johns Hopkins University School of Medicine, 5510 Nathan Shock Dr, Baltimore, MD 21224 ( rvandrey@ 123456jhmi.edu ).
                Author Contributions: Drs Spindle and Vandrey had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Spindle, Cone, Mitchell, Bigelow, Hayes, Vandrey.
                Acquisition, analysis, or interpretation of data: Spindle, Cone, Schlienz, Mitchell, Bigelow, Flegel, Vandrey.
                Drafting of the manuscript: Spindle, Schlienz, Vandrey.
                Critical revision of the manuscript for important intellectual content:  Cone, Schlienz, Mitchell, Bigelow, Flegel, Hayes, Vandrey.
                Statistical analysis: Spindle, Vandrey.
                Obtained funding: Mitchell, Flegel, Hayes, Vandrey.
                Administrative, technical, or material support: Cone, Schlienz, Mitchell, Bigelow, Flegel, Hayes.
                Supervision: Cone, Schlienz, Bigelow, Vandrey.
                Conflict of Interest Disclosures: Dr Vandrey reported receiving personal fees and has served as a consultant or received honoraria from Zynerba Pharmaceuticals, Insys Therapeutics, Battelle Memorial Institute, and Canopy Health Innovations Inc outside the submitted work. Drs Vandrey and Spindle reported receiving grants from the Substance Abuse and Mental Health Services Administration (SAMHSA) during the conduct of the study. Dr Cone reported serving as a consultant for ConeChem Research, LLC and RTI during the conduct of the study. Dr Schlienz reported grants from the National Institute on Drug Abuse outside the submitted work. Dr Mitchell reported grants from SAMHSA during the conduct of the study. Dr Hayes reported receiving funding from the Department of Health and Human Services, SAMHSA, National Laboratory Certification Program, and RTI International during the conduct of the study. No other disclosures were reported.
                Funding/Support: This study was funded by the Substance Abuse and Mental Health Services Administration.
                Role of the Funder/Sponsor: The funder provided technical assistance on the design and conduct of the study; analysis and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. The funders had no role in the collection or management of the study data.
                Data Sharing Statement: See Supplement 3.
                Additional Contributions: We thank the support staff of the Johns Hopkins University Behavioral Pharmacology Research Unit for outstanding contributions to the implementation of this study. Christine Moore, PhD, and Cynthia Coulter, BS, TC-NRCC, performed analytic testing (liquid chromatography–mass spectrometry analyses) for Δ9-tetrahydrocannabinol in blood samples. They are employees of Immunoanalysis, Inc, and were not compenstated for their services provided in this study.
                Article
                zoi180211
                10.1001/jamanetworkopen.2018.4841
                6324384
                30646391
                15ae532c-54af-4186-af95-76f7c2158d50
                Copyright 2018 Spindle TR et al. JAMA Network Open .

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 12 July 2018
                : 26 September 2018
                : 28 September 2018
                Categories
                Research
                Original Investigation
                Featured
                Online Only
                Substance Use and Addiction

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