{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:07:00Z","timestamp":1771297620368,"version":"3.50.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Canopy Growth Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Due to a lack of published pharmacokinetic (PK) and\/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of cannabis for medical purposes is limited. This Phase 1, multiple-dose study evaluated the safety, tolerability, PK and PD of Spectrum Red softgels (2.5\u2009mg \u03949-tetrahydrocannabinol (THC) and &amp;lt;0.25\u2009mg cannabidiol (CBD)). Participants (n\u2009=\u200941) were randomized to one of five groups: 5\u2009mg THC and 0.06\u2009mg CBD daily (Treatment A), 10\u2009mg THC and 0.12\u2009mg CBD daily (Treatment B), 15\u2009mg THC and 0.18\u2009mg CBD daily (Treatment C), 20\u2009mg THC and 0.24\u2009mg CBD daily (Treatment D) or placebo. Study medication was administered in divided doses, every 12\u2009h, \u223c60\u2009min after a standardized meal, for 7 consecutive days. All treatment-emergent adverse events (TEAEs) (65\/65) were of mild-to-moderate severity; none was serious. The highest number of TEAEs (30\/65) occurred on the first day of treatment. The most common TEAEs included somnolence, lethargy and headache (reported by eight, seven and five participants, respectively). On Day 7, maximum observed plasma concentration of 11-carboxy-THC increased by 2.0- and 2.5-fold as the dose doubled between Treatments A and B and between Treatments B and D, respectively. Mean peak post-treatment ratings of self-reported subjective effects of \u2018feel any effect\u2019 and \u2018dazed\u2019 differed between Treatment D and placebo on Days 1, 3 and 7. Over a week of twice-daily dosing of Spectrum Red softgels, daily doses of THC up to 20\u2009mg and of CBD up to 0.24\u2009mg were generally safe and became better tolerated after the first day of treatment. A prudent approach to improve tolerability with Spectrum Red softgels might involve initial daily doses no higher than 10\u2009mg THC and 0.12\u2009mg CBD in divided doses, with titration upward over time as needed based on tolerability.<\/jats:p>","DOI":"10.1093\/jat\/bkab035","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T20:40:26Z","timestamp":1618346426000},"page":"528-539","source":"Crossref","is-referenced-by-count":8,"title":["Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Red Softgels in Healthy Participants"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-9819","authenticated-orcid":false,"given":"Erica N","family":"Peters","sequence":"first","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Mosesova","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"MacNair","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Vandrey","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Hunter","family":"Land","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A","family":"Ware","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Turcotte","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel O","family":"Bonn-Miller","sequence":"additional","affiliation":[{"name":"Canopy Growth Corporation, One Hershey Drive, Smiths Falls, K7A 0A8 ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"2022052020215519600_R1","article-title":"The medical use of cannabis for reducing morbidity and mortality in patients with HIV\/AIDS","volume":"4","author":"Lutge","year":"2013","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"2022052020215519600_R2","article-title":"Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy","volume":"11","author":"Smith","year":"2015","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"2022052020215519600_R3","article-title":"Cannabis-based medicines for chronic neuropathic pain in adults","volume":"3","author":"Mucke","year":"2018","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"2022052020215519600_R4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1089\/can.2019.0037","article-title":"Human pharmacokinetic parameters of orally administered delta(9)-tetrahydrocannabinol capsules are altered by fed versus fasted conditions and sex differences","volume":"4","author":"Lunn","year":"2019","journal-title":"Cannabis and Cannabinoid Research"},{"key":"2022052020215519600_R5","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/clpt.1980.181","article-title":"Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking","volume":"28","author":"Ohlsson","year":"1980","journal-title":"Clinical Pharmacology Therapeutics"},{"key":"2022052020215519600_R6","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1007\/BF02085029","article-title":"Interactions of delta 1-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. 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