Cited by 288Cannabis and Cannabinoid ResearchComplementary and Alternative Medicine StudiesPsychedelics and Drug Studies

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Cannabinoids in Clinical Practice

Williamson, Elizabeth M., Evans, Fred J.·2000·Drugs

DOI 10.2165/00003495-200060060-00005

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Abstract

Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette's syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.

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Perrotin-Brunel, H., Kroon, M. C., van Roosmalen, M. J. E., van Spronsen, J., Peters, C. J., & Witkamp, G.-J. (2010) · The Journal of Supercritical Fluids · doi:10.1016/j.supflu.2010.09.011 · Cited by 90
Medicinal cannabis: is Δ9–tetrahydrocannabinol necessary for all its effects?
Wilkinson, J. D., Whalley, B. J., Baker, D., Pryce, G., Constanti, A., Gibbons, S., & Williamson, E. M. (2003) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357022304 · Cited by 89
Self-citation
Validated method for the simultaneous determination of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography–mass spectrometry with positive chemical ionization
GUSTAFSON, R., Moolchan, E. T., Barnes, A. J., LEVINE, B. S., & HUESTIS, M. (2003) · Journal of Chromatography B · doi:10.1016/j.jchromb.2003.09.022 · Cited by 85
Cannabis for Inflammatory Bowel Disease
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Single episode of maternal deprivation and adult depressive profile in mice: interaction with cannabinoid exposure during adolescence
Macrı̀, S., & Laviola, G. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.02.009 · Cited by 81
ROLE OF DORSAL HIPPOCAMPAL CANNABINOID RECEPTORS AND NITRIC OXIDE IN ANXIETY LIKE BEHAVIOURS IN RATS USING THE ELEVATED PLUS‐MAZE TEST
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Chemistry of Cannabis
Hazekamp, A., Fischedick, J. T., Díez, M. L., Lubbe, A., & Ruhaak, L. R. (2010) · Elsevier eBooks · doi:10.1016/b978-008045382-8.00091-5 · Cited by 77
Nutraceuticals and Headache: The Biological Basis
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“CBN is an oxidation product of THC and an indication of deterioration.(144) This research group then assessed cannabinoids for their ability to inhibit agonist-induced platelet aggregation and [14C]5-HT release.”
BackgroundInfluential
Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models
Patel, N., Kommineni, N., Surapaneni, S. K., Kalvala, A. K., Yaun, X., Gebeyehu, A., Arthur, P., Duke, L. C., York, S. B., Bagde, A., et al. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120943 · Cited by 73
Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: The role of the endocannabinoid system
Wang, H., Wang, L., Zhang, R., Chen, Y.-C., Liu, L., Gao, F., Nie, H., Hou, W., Peng, Z., & Tan, Q. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.01.004 · Cited by 70
“The idea that the endocannabinoid system may be involved in depression is rooted in the fact that consumption of cannabis in humans has profound effects upon mood (Williamson and Evans, 2000).”
Effect of Induced Polyploidy on Some Biochemical Parameters in Cannabis sativa L.
Bagheri, M., & Mansouri, H. (2014) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-014-1435-8 · Cited by 69
Altering endocannabinoid neurotransmission at critical developmental ages: impact on rodent emotionality and cognitive performance
Trezza, V., Campolongo, P., Manduca, A., Morena, M., Palmery, M., Vanderschuren, L. J. M. J., & Cuomo, V. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00002 · Cited by 69
“It has indeed repeatedly been shown that cannabis exposure produces a wide range of subjective emotional effects in humans (Tunving, 1985; Williamson and Evans, 2000; Degenhardt et al., 2003; Di Forti et al., 2007; Murray et al., 2007; Fattore and Fratta, 2011).”
Background
Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation
Vincent, L., Vang, D., Nguyen, J., Benson, B. A., Lei, J.-X., & Gupta, K. (2015) · Haematologica · doi:10.3324/haematol.2015.136523 · Cited by 68
Elicitation studies in cell suspension cultures of Cannabis sativa L.
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Involvement of κ/Dynorphin System in WIN 55,212-2 Self-Administration in Mice
Mendizábal, V. E., Zimmer, A., & Maldonado, R. J. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300957 · Cited by 75
The Use of Cannabis for Headache Disorders
Lochte, B. C., Beletsky, A., Samuel, N., & Grant, I. (2017) · Cannabis and Cannabinoid Research · doi:10.1089/can.2016.0033 · Cited by 68
The abuse potential of the synthetic cannabinoid nabilone
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“Current evidence from epidemiological studies suggests that patients who have tried oral ingestion of isolated cannabinoids find smoked cannabis more effective [21], with fewer unwanted effects [22].”
Background
Comorbid cannabis use and panic disorder: short term and long term follow‐up study
Dannon, P. N., Lowengrub, K., Amiaz, R., Grunhaus, L. J., & Kotler, M. (2004) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.560 · Cited by 66
The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives
Marco, E. M., & Laviola, G. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111408459 · Cited by 67
“However, the therapeutic use of cannabinoids can also be accompanied by adverse reactions such as panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children (Croxford 2003; Williamson and Evans, 2000).”
Background
Cannabinoids concentration variability in cannabis olive oil galenic preparations
Carcieri, C., Tomasello, C., Simiele, M., Nicolò, A. D., Avataneo, V., Canzoneri, L., Cusato, J., Perri, G. D., & D’Avolio, A. (2017) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12845 · Cited by 64
“Preparation protocol for APIs extraction sometimes included a preheating step, to enhance the yield of decarboxylation of acid-APIs (THCA, CBDA): this optional step, and the lack of a standardized temperature and time, greatly contributes to a possibly clinically relevant interlot variability in APIs concentrations (F…”
Background
Enhancement of endocannabinoid signalling during adolescence: Modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats
Marco, E. M., Adriani, W., Canese, R., Podo, F., Viveros, M., & Laviola, G. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.10.006 · Cited by 62
Design, Synthesis and Biological Activity of Rigid Cannabinoid CB1 Receptor Antagonists.
Stoit, A. R., Lange, J. H. M., den Hartog, A. P., Ronken, E., Tipker, K., van Stuivenberg, H. H., Dijksman, J. A. R., Wals, H. C., & Kruse, C. G. (2002) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.50.1109 · Cited by 61
Clinical Management of Pain in Advanced Lung Cancer
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TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids
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Examining the roles of cannabinoids in pain and other therapeutic indications: a review
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“In more recent years, cannabinoids have once again been suggested as possible therapeutic agents for countless medical conditions [8-11].”
Background
Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice
Wiley, J. L., Lefever, T. W., Marusich, J. A., Grabenauer, M., Moore, K. N., Huffman, J. W., & Thomas, B. F. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.016 · Cited by 58
“In fact, higher doses of THC have been associated with anxiety and dysphoria in anecdotal reports and a laboratory study (Hunault et al., 2014; Williamson and Evans, 2000).”
Sex differences in behavioral effects of cannabinoids
Craft, R. M. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.04.019 · Cited by 58
Studies on the metabolism of the Δ9‐tetrahydrocannabinol precursor Δ9‐tetrahydrocannabinolic acid A (Δ9‐THCA‐A) in rat using LC‐MS/MS, LC‐QTOF MS and GC‐MS techniques
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An evaluation of the quality of medicinal grade cannabis in the Netherlands
Hazekamp, A. (2006) · Cited by 57
Rational Design and Synthesis of an Orally Active Indolopyridone as a Novel Conformationally Constrained Cannabinoid Ligand Possessing Antiinflammatory Properties
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A qualitative and quantitative HPTLC densitometry method for the analysis of cannabinoids in Cannabis sativa L.
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Efficient one-pot synthetic approaches for cannabinoid analogues and their application to biologically interesting (−)-hexahydrocannabinol and (+)-hexahydrocannabinol
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Detection and identification of Cannabis sativa L. using near infrared hyperspectral imaging and machine learning methods. A feasibility study
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Anticoagulant effects of a Cannabis extract in an obese rat model
Coetzee, C., Levendal, R. ‐., van de Venter, M., & Frost, C. L. (2006) · Phytomedicine · doi:10.1016/j.phymed.2006.02.004 · Cited by 53

Authors: Williamson, E. M., & Evans, F. J.
Affiliations: University of London (GB)
ORCID: Williamson, Elizabeth M.
Venue: Drugs
Publisher: Springer Science and Business Media LLC
Published: 2000-12
Volume: 60
Issue: 6
Pages: 1303-1314
ISSN: 0012-6667 (ISSN-L)
DOI: 10.2165/00003495-200060060-00005
OpenAlex: W2057393616
Cited by: 283
References: 90
Citations by year: 2026: 5 · 2025: 9 · 2024: 8 · 2023: 5 · 2022: 12 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 10
FWCI: 1.52
Type: journal article
Language: en
Open access: closed
Locations: Drugs (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Keywords: cannabinoids, tetrahydrocannabinol, cannabidiol, cannabigerol, cannabis, multiple sclerosis, muscle spasm, pain, nabilone, chemotherapy-induced nausea and vomiting, traumatic brain injury, migraine, Tourette syndrome, glaucoma, asthma, cannabis safety, adverse effects, driving impairment, alcohol interaction, cannabinoid receptors
MeSH terms: Animals, Asthma, Blood Pressure, Cannabinoids, Cannabis, Glaucoma, Humans, Nervous System Diseases, Placebo Effect

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