• Alexander Shustorovich, Jamie Corroon, Mark S Wallace, and Michelle Sexton.
• Department of Physical Medicine & Rehabilitation, JFK Johnson Rehabilitation Institute, 65 James St Edison, NJ 08820, USA.
• Pain Med. 2024 Jan 24.

IntroductionCannabinoids are being used by patients to help with chronic pain management and to address the two primary chronic pain comorbidities of anxiety and sleep disturbance. It is necessary to understand the biphasic effects of cannabinoids to improve treatment of this symptom triad.MethodsA scoping review was conducted to identify whether biphasic effects of cannabinoids on pain severity, anxiolysis, and sleep disturbance have been reported. The search included Embase, Biosis and Medline databases of clinical literature published between 1970-2021. The inclusion criteria were: 1) adults over 18 years of age; 2) data or discussion of dose effects associated with u-shaped or linear dose responses and 3) measurements of pain and/or anxiety and/or sleep disturbance. Data were extracted by two independent reviewers (third reviewer used as a tiebreaker) and subjected to a thematic analysis.ResultsAfter database search and study eligibility assessment, 44 publications met the final criteria for review. 18 publications that specifically provided information on dose response were included in the final synthesis: 9 related to pain outcomes, 7 measuring anxiety, and 2 reporting sleep effects.ConclusionsThis scoping review reports on biphasic effects of cannabinoids related to pain, sleep, and anxiety. Dose response relationships are present, but we found gaps in the current literature for biphasic effects of cannabinoids in humans. There is a lack of prospective research in humans exploring this specific relationship.© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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