Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

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Abstract

Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

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Most cited references 129

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Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication.

Ronald C Kessler, Wai Tat Chiu, Olga Demler … (2005)

Little is known about the general population prevalence or severity of DSM-IV mental disorders. To estimate 12-month prevalence, severity, and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders in the recently completed US National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using a fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents 18 years and older. Twelve-month DSM-IV disorders. Twelve-month prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%; substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses. Latent class analysis detected 7 multivariate disorder classes, including 3 highly comorbid classes representing 7% of the population. Although mental disorders are widespread, serious cases are concentrated among a relatively small proportion of cases with high comorbidity.

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painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.

Ralf Baron, Rainer Freynhagen, Thomas R. Tölle … (2006)

Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities. In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD-Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients. The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co-morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component. Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.

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The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.

R Pertwee (2008)

Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact with cannabinoid CB1 and CB2 receptors. Delta9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Delta9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Delta9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by delta9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which delta9-THC, CBD and delta9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.

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Author and article information

Contributors

Jeremy D. Henson:

ORCID: http://orcid.org/0000-0002-1594-9310

j.henson@unsw.edu.au

Luis Vitetta:

ORCID: http://orcid.org/0000-0002-7490-9298

luis.vitetta@sydney.edu.au

Sean Hall:

ORCID: http://orcid.org/0000-0003-0090-7895

sean_hall@medlab.co

Journal

Journal ID (nlm-ta): Inflammopharmacology

Journal ID (iso-abbrev): Inflammopharmacology

Title: Inflammopharmacology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0925-4692

ISSN (Electronic): 1568-5608

Publication date (Electronic): 7 July 2022

Publication date PMC-release: 7 July 2022

Publication date (Print): 2022

Volume: 30

Issue: 4

Pages: 1167-1178

Affiliations

[1 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, Prince of Wales Clinical School, , University of NSW, ; Sydney, NSW 2052 Australia

[2 ]Medlab Clinical Ltd, Sydney, NSW 2015 Australia

[3 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, Faculty of Medicine and Health, , The University of Sydney, ; Sydney, NSW 2006 Australia

Author information

Jeremy D. Henson http://orcid.org/0000-0002-1594-9310

Luis Vitetta http://orcid.org/0000-0002-7490-9298

Sean Hall http://orcid.org/0000-0003-0090-7895

Article

Publisher ID: 1020

DOI: 10.1007/s10787-022-01020-z

PMC ID: 9294022

PubMed ID: 35796920

SO-VID: 792527fb-2acc-42d0-a7d5-7376c10dc56f

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 2 June 2022

Date accepted : 13 June 2022

Funding

Funded by: University of New South Wales

Open Access :

Open Access funding enabled and organized by CAUL and its Member Institutions

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: tetrahydrocannabinol,cannabidiol,pain,stress,anxiety,depression,insomnia

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: tetrahydrocannabinol, cannabidiol, pain, stress, anxiety, depression, insomnia

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

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Most cited references 129

Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication.

painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.

The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.

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