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Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment

Educational Objective
To use federally compatible, observational methods to study high–Δ9-tetrahydrocannabinol (THC) legal market forms of cannabis.
1 Credit CME
Key Points

Question  What is the association of legal market cannabis flower and concentrates with cannabis intoxication and neurobehavioral impairment?

Findings  In this cohort study of 121 cannabis flower users and concentrate users randomly assigned to higher- vs lower-THC products within user groups, use of legal market cannabis concentrates (ranging from 70%-90% tetrahydrocannabinol [THC]) produced significantly higher THC blood plasma levels compared with use of legal market cannabis flower (ranging from 16%-24% THC). Despite differences in THC exposure, flower and concentrate users showed similar neurobehavioral patterns after acute cannabis use and the domains of verbal memory and proprioception-focused postural stability for both groups were associated with THC.

Meaning  Use of cannabis concentrates was associated with higher THC exposure and potentially greater risk, but differences in short-term subjective and neurobehavioral impairments did not track specifically with strength of the cannabis consumed.


Importance  The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research.

Objective  To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis.

Design, Setting, and Participants  In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study’s cannabis use instructions and had complete data across primary outcomes.

Exposures  Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary.

Main Outcomes and Measures  Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance.

Results  A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC’s active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) μg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) μg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed.

Conclusions and Relevance  This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users’ domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: March 11, 2020.

Corresponding Author: L. Cinnamon Bidwell, PhD, Institute of Cognitive Science, UCB 344, Boulder, CO 80309 9(

Published Online: June 10, 2020. doi:10.1001/jamapsychiatry.2020.0927

Author Contributions: Drs Bidwell and Hutchison had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bidwell, Tracy, Bryan, Hutchison.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Bidwell, Ellingson, Karoly, YorkWilliams, Hitchcock, Tracy, Bryan, Hutchison.

Critical revision of the manuscript for important intellectual content: Bidwell, Ellingson, YorkWilliams, Hitchcock, Tracy, Klawitter, Sempio, Bryan, Hutchison.

Statistical analysis: Bidwell, Ellingson, Karoly, YorkWilliams, Hitchcock, Tracy, Bryan, Hutchison.

Obtained funding: Bidwell, Bryan, Hutchison.

Administrative, technical, or material support: Bidwell, Hitchcock, Tracy, Klawitter, Hutchison.

Supervision: Bidwell, Tracy, Hutchison.

Conflict of Interest Disclosures: Dr Bidwell reported grants from the National Institutes of Health (NIH)/National Institute on Drug Abuse and the State of Colorado Department of Public Health and Environment during the conduct of the study. Dr Ellingson reported grants from the NIH during the conduct of the study. Dr Klawitter reported grants from the Colorado Department of Public Health and Environment and NIH during the conduct of the study. Dr Sempio reported grants from the Colorado Department of Public Health and Environment and the NIH during the conduct of the study. Dr Bryan reported grants from the NIH and State of Colorado during the conduct of the study. No other disclosures were reported.

Funding/Support: Funding for this study was provided by grants from the NIH (DA039707 to Dr Hutchison) and Colorado Department of Public Health and Environment (96947 to Dr Bidwell).

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Vergara  D , Bidwell  LC , Gaudino  R ,  et al.  Compromised external validity: federally produced cannabis does not reflect legal markets.   Sci Rep. 2017;7(March):46528. doi:10.1038/srep46528 PubMedGoogle ScholarCrossref
Orens  A , Light  M , Lewandowski  B , Rowberry  J , Saloga  C . 2017 market update. Accessed August 20, 2018.
Stogner  JM , Miller  BL .  Assessing the dangers of “dabbing”: mere marijuana or harmful new trend?   Pediatrics. 2015;136(1):1-3. doi:10.1542/peds.2015-0454 PubMedGoogle ScholarCrossref
Daniulaityte  R , Lamy  FR , Barratt  M ,  et al.  Characterizing marijuana concentrate users: a web-based survey.   Drug Alcohol Depend. 2017;178:399-407. doi:10.1016/j.drugalcdep.2017.05.034 PubMedGoogle ScholarCrossref
Raber  JC , Elzinga  S , Kaplan  C .  Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing.   J Toxicol Sci. 2015;40(6):797-803. doi:10.2131/jts.40.797 PubMedGoogle ScholarCrossref
Cinnamon Bidwell  L , YorkWilliams  SL , Mueller  RL , Bryan  AD , Hutchison  KE .  Exploring cannabis concentrates on the legal market: User profiles, product strength, and health-related outcomes.   Addict Behav Rep. 2018;8:102-106. doi:10.1016/j.abrep.2018.08.004 PubMedGoogle ScholarCrossref
Volkow  ND , Baler  RD , Compton  WM , Weiss  SRB .  Adverse health effects of marijuana use.   N Engl J Med. 2014;370(23):2219-2227. doi:10.1056/NEJMra1402309 PubMedGoogle ScholarCrossref
Heishman  SJ , Huestis  MA , Henningfield  JE , Cone  EJ .  Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures.   Pharmacol Biochem Behav. 1990;37(3):561-565. doi:10.1016/0091-3057(90)90028-G PubMedGoogle ScholarCrossref
Chait  LD , Zacny  JP .  Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans.   Psychopharmacology (Berl). 1992;107(2-3):255-262. doi:10.1007/BF02245145 PubMedGoogle ScholarCrossref
Chait  LD , Evans  SM , Grant  KA , Kamien  JB , Johanson  CE , Schuster  CR .  Discriminative stimulus and subjective effects of smoked marijuana in humans.   Psychopharmacology (Berl). 1988;94(2):206-212. doi:10.1007/BF00176846 PubMedGoogle ScholarCrossref
Martin-Santos  R , Crippa  JA , Batalla  A ,  et al.  Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.   Curr Pharm Des. 2012;18(32):4966-4979. doi:10.2174/138161212802884780 PubMedGoogle ScholarCrossref
Hunault  CC , Böcker  KBE , Stellato  RK , Kenemans  JL , de Vries  I , Meulenbelt  J .  Acute subjective effects after smoking joints containing up to 69 mg Δ9-tetrahydrocannabinol in recreational users: a randomized, crossover clinical trial.   Psychopharmacology (Berl). 2014;231(24):4723-4733. doi:10.1007/s00213-014-3630-2 PubMedGoogle ScholarCrossref
Hart  CL , van Gorp  W , Haney  M , Foltin  RW , Fischman  MW .  Effects of acute smoked marijuana on complex cognitive performance.   Neuropsychopharmacology. 2001;25(5):757-765. doi:10.1016/S0893-133X(01)00273-1 PubMedGoogle ScholarCrossref
Schacht  JP , Selling  RE , Hutchison  KE .  Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis.   Psychopharmacology (Berl). 2009;203(3):511-517. doi:10.1007/s00213-008-1397-z PubMedGoogle ScholarCrossref
Cooper  ZD , Haney  M .  Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor.   Addict Biol. 2008;13(2):188-195. doi:10.1111/j.1369-1600.2007.00095.x PubMedGoogle ScholarCrossref
Metrik  J , Kahler  CW , Reynolds  B ,  et al.  Balanced placebo design with marijuana: pharmacological and expectancy effects on impulsivity and risk taking.   Psychopharmacology (Berl). 2012;223(4):489-499. doi:10.1007/s00213-012-2740-y PubMedGoogle ScholarCrossref
Metrik  J , Rohsenow  DJ , Monti  PM ,  et al.  Effectiveness of a marijuana expectancy manipulation: Piloting the balanced-placebo design for marijuana.   Exp Clin Psychopharmacol. 2009;17(4):217-225. doi:10.1037/a0016502 PubMedGoogle ScholarCrossref
Heishman  SJ , Stitzer  ML , Yingling  JE .  Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance.   Pharmacol Biochem Behav. 1989;34(1):173-179. doi:10.1016/0091-3057(89)90369-9 PubMedGoogle ScholarCrossref
Cappell  H , Pliner  P .  Regulation of the self-administration of marihuana by psychological and pharmacological variables.   Psychopharmacologia. 1974;40(1):65-76. doi:10.1007/BF00429448 PubMedGoogle ScholarCrossref
Ramesh  D , Haney  M , Cooper  ZD .  Marijuana’s dose-dependent effects in daily marijuana smokers.   Exp Clin Psychopharmacol. 2013;21(4):287-293. doi:10.1037/a0033661 PubMedGoogle ScholarCrossref
Cooper  ZD , Haney  M .  Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts.   Drug Alcohol Depend. 2009;103(3):107-113. doi:10.1016/j.drugalcdep.2009.01.023 PubMedGoogle ScholarCrossref
Hartman  RL , Brown  TL , Milavetz  G ,  et al.  Controlled cannabis vaporizer administration: blood and plasma cannabinoids with and without alcohol.   Clin Chem. 2015;61(6):850-869. doi:10.1373/clinchem.2015.238287 PubMedGoogle Scholar
Huestis  MA , Henningfield  JE , Cone  EJ .  Blood cannabinoids. I. absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana.   J Anal Toxicol. 1992;16(5):276-282. doi:10.1093/jat/16.5.276PubMedGoogle Scholar
Karila  L , Roux  P , Rolland  B ,  et al. Acute and long-term effects of cannabis use: a review. Accessed January 24, 2019.
Volkow  ND , Swanson  JM , Evins  AE ,  et al.  Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review.   JAMA Psychiatry. 2016;73(3):292-297. doi:10.1001/jamapsychiatry.2015.3278 PubMedGoogle Scholar
Broyd  SJ , van Hell  HH , Beale  C , Yücel  M , Solowij  N .  Acute and chronic effects of cannabinoids on human cognition—a systematic review.   Biol Psychiatry. 2016;79(7):557-567. doi:10.1016/j.biopsych.2015.12.002 PubMedGoogle Scholar
Crean  RD , Crane  NA , Mason  BJ .  An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions.   J Addict Med. 2011;5(1):1-8. doi:10.1097/ADM.0b013e31820c23fa PubMedGoogle Scholar
Crane  NA , Schuster  RM , Fusar-Poli  P , Gonzalez  R .  Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences.   Neuropsychol Rev. 2013;23(2):117-137. doi:10.1007/s11065-012-9222-1 PubMedGoogle Scholar
Ranganathan  M , D’Souza  DC .  The acute effects of cannabinoids on memory in humans: a review.   Psychopharmacology (Berl). 2006;188(4):425-444. doi:10.1007/s00213-006-0508-y PubMedGoogle Scholar
Lundqvist  T .  Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions.   Pharmacol Biochem Behav. 2005;81(2):319-330. doi:10.1016/j.pbb.2005.02.017 PubMedGoogle Scholar
Ramaekers  JG , Kauert  G , van Ruitenbeek  P , Theunissen  EL , Schneider  E , Moeller  MR .  High-potency marijuana impairs executive function and inhibitory motor control.   Neuropsychopharmacology. 2006;31(10):2296-2303. doi:10.1038/sj.npp.1301068 PubMedGoogle Scholar
Stella  N .  Chronic THC intake modifies fundamental cerebellar functions.   J Clin Invest. 2013;123(8):3208-3210. doi:10.1172/JCI70226 PubMedGoogle Scholar
Pillay  SS , Rogowska  J , Kanayama  G ,  et al.  Cannabis and motor function: fMRI changes following 28 days of discontinuation.   Exp Clin Psychopharmacol. 2008;16(1):22-32. doi:10.1037/1064-1297.16.1.22 PubMedGoogle Scholar
Klawitter  J , Sempio  C , Mörlein  S ,  et al.  An atmospheric pressure chemical ionization MS/MS assay using online extraction for the analysis of 11 cannabinoids and metabolites in human plasma and urine.   Ther Drug Monit. 2017;39(5):556-564. doi:10.1097/FTD.0000000000000427 PubMedGoogle Scholar
Huestis  MA , Sampson  AH , Holicky  BJ , Henningfield  JE , Cone  EJ .  Characterization of the absorption phase of marijuana smoking.   Clin Pharmacol Ther. 1992;52(1):31-41. doi:10.1038/clpt.1992.100 PubMedGoogle Scholar
Haertzen  CA , Hickey  JE . Addiction Research Center Inventory (ARCI): measurement of euphoria and other drug effects. Accessed January 1, 2016.
Zuardi  AW , Shirakawa  I , Finkelfarb  E , Karniol  IG .  Action of cannabidiol on the anxiety and other effects produced by δ 9-THC in normal subjects.   Psychopharmacology (Berl). 1982;76(3):245-250. doi:10.1007/BF00432554 PubMedGoogle Scholar
Bidwell  LC , Mueller  R , YorkWilliams  SL , Hagerty  S , Bryan  AD , Hutchison  KE .  A novel observational method for assessing acute responses to cannabis: preliminary validation using legal market strains.   Cannabis Cannabinoid Res. 2018;3(1):35-44. doi:10.1089/can.2017.0038 PubMedGoogle Scholar
Shacham  S .  A shortened version of the profile of mood states.   J Pers Assess. 1983;47(3):305-306. doi:10.1207/s15327752jpa4703_14 PubMedGoogle Scholar
Metrik  J , Kahler  CW , McGeary  JE , Monti  PM , Rohsenow  DJ .  Acute effects of marijuana smoking on negative and positive affect.   J Cogn Psychother. 2011;25(1):31-46. doi:10.1891/0889-8391.25.1.31 PubMedGoogle Scholar
Hindocha  C , Freeman  TP , Xia  JX , Shaban  NDC , Curran  HV .  Acute memory and psychotomimetic effects of cannabis and tobacco both ‘joint’ and individually: a placebo-controlled trial.   Psychol Med. 2017;47(15):2708-2719. doi:10.1017/S0033291717001222 PubMedGoogle Scholar
Panee  J , Gerschenson  M , Chang  L .  Associations between microbiota, mitochondrial function, and cognition in chronic marijuana users.   J Neuroimmune Pharmacol. 2018;13(1):113-122. doi:10.1007/s11481-017-9767-0 PubMedGoogle Scholar
Petker  T , Owens  MM , Amlung  MT , Oshri  A , Sweet  LH , MacKillop  J .  Cannabis involvement and neuropsychological performance: findings from the Human Connectome Project.   J Psychiatry Neurosci. 2019;44(6):414-422. doi:10.1503/jpn.180115 PubMedGoogle Scholar
Thompson  TAC , Wilson  PH , Snyder  PJ ,  et al.  Sensitivity and test-retest reliability of the international shopping list test in assessing verbal learning and memory in mild Alzheimer’s disease.   Arch Clin Neuropsychol. 2011;26(5):412-424. doi:10.1093/arclin/acr039 PubMedGoogle Scholar
Weintraub  S , Dikmen  SS , Heaton  RK ,  et al.  Cognition assessment using the NIH Toolbox.   Neurology. 2013;80(11)(suppl 3):S54-S64. doi:10.1212/WNL.0b013e3182872ded PubMedGoogle Scholar
Weintraub  S , Dikmen  SS , Heaton  RK ,  et al.  The cognition battery of the NIH toolbox for assessment of neurological and behavioral function: validation in an adult sample.   J Int Neuropsychol Soc. 2014;20(6):567-578. doi:10.1017/S1355617714000320 PubMedGoogle Scholar
Bosker  WM , Kuypers  KPC , Theunissen  EL ,  et al.  Medicinal Δ(9)–tetrahydrocannabinol (dronabinol) impairs on-the-road driving performance of occasional and heavy cannabis users but is not detected in standard field sobriety tests.   Addiction. 2012;107(10):1837-1844. doi:10.1111/j.1360-0443.2012.03928.x PubMedGoogle Scholar
Hirvonen  J , Goodwin  RS , Li  C-T ,  et al.  Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.   Mol Psychiatry. 2012;17(6):642-649. doi:10.1038/mp.2011.82 PubMedGoogle Scholar
Yao  B , Mackie  K .  Endocannabinoid receptor pharmacology.   Curr Top Behav Neurosci. 2009;1:37-63. doi:10.1007/978-3-540-88955-7_2 PubMedGoogle Scholar
Flanagan  JM , Gerber  AL , Cadet  JL , Beutler  E , Sipe  JC .  The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction.   Hum Genet. 2006;120(4):581-588. doi:10.1007/s00439-006-0250-x PubMedGoogle Scholar
Cravatt  BF , Giang  DK , Mayfield  SP , Boger  DL , Lerner  RA , Gilula  NB .  Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides.   Nature. 1996;384(6604):83-87. doi:10.1038/384083a0 PubMedGoogle Scholar
Huestegge  L , Radach  R , Kunert  HJ .  Long-term effects of cannabis on oculomotor function in humans.   J Psychopharmacol. 2009;23(6):714-722. doi:10.1177/0269881108091601 PubMedGoogle Scholar
Zuurman  L , Roy  C , Schoemaker  RC ,  et al.  Effect of intrapulmonary tetrahydrocannabinol administration in humans.   J Psychopharmacol. 2008;22(7):707-716. doi:10.1177/0269881108089581 PubMedGoogle Scholar
Klumpers  LE , Beumer  TL , van Hasselt  JGC ,  et al.  Novel Δ(9)–tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects.   Br J Clin Pharmacol. 2012;74(1):42-53. doi:10.1111/j.1365-2125.2012.04164.x PubMedGoogle Scholar
Greenberg  HS , Werness  SAS , Pugh  JE , Andrus  RO , Anderson  DJ , Domino  EF .  Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers.   Clin Pharmacol Ther. 1994;55(3):324-328. doi:10.1038/clpt.1994.33 PubMedGoogle Scholar
Hafstrom  A , Patel  M , Modig  F , Magnusson  M , Fransson  PA .  Acute alcohol intoxication impairs segmental body alignment in upright standing.   J Vestib Res. 2014;24(4):297-304. doi:10.3233/VES-140513 PubMedGoogle Scholar
Liguori  A , Gatto  CP , Jarrett  DB .  Separate and combined effects of marijuana and alcohol on mood, equilibrium and simulated driving.   Psychopharmacology (Berl). 2002;163(3-4):399-405. doi:10.1007/s00213-002-1124-0 PubMedGoogle Scholar
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