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Cited by 462Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsPain Management and Opioid Use

Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial

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Ellis, Ronald J, Toperoff, Will, Vaida, Florin, van den Brande, Geoffrey, Gonzales, James, Gouaux, Ben, Bentley, Heather, Atkinson, J Hampton·2009·Neuropsychopharmacology
DOI 10.1038/npp.2008.120PMC PMC3066045
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Abstract

Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Delta-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p=0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.

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  • This study found no changes in heart rate, blood pressure, plasma HIV RNA, or blood CD4+ lymphocyte counts following cannabis treatment, suggesting that cannabis did not negatively impact the already compromised immune system in these patients.

    “This study found no changes in heart rate, blood pressure, plasma HIV RNA (viral load; VL), or blood CD4+ lymphocyte counts following cannabis treatment, suggesting that cannabis did not negatively impact the already compromised immune system in these patients.”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [137]

  • Ellis and colleagues reported similar results in a crossover study employing multiple concentrations of Δ9-THC in cannabis cigarettes; cannabis was superior to placebo in either phase as measured with the descriptor differential scale or visual analogue scale.

    “In 2009, Ellis and colleagues137 reported similar results in a crossover study employing multiple concentrations of Δ9-THC in cannabis cigarettes administered to patients. Cannabis was superior to placebo in either phase of the crossover as measured with the descriptor differential scale (DDS) or VAS.”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [137]

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  1. Lingjaerde O Ahlfors UG Bech P Dencker SJ Elgen K The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients Acta Psychiatr Scand Suppl 1987b 334 1 100 2887090

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Authors
Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G., Gonzales, J., Gouaux, B., Bentley, H., & Atkinson, J. H.
Affiliations
University of California San Diego (US)
Corresponding author
Ellis, Ronald J
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2008-08-06
Volume
34
Issue
3
Pages
672-680
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2008.120
PMC
PMC3066045
OpenAlex
W2123945136
Cited by
461
References
47
Citations by year
2026: 9 · 2025: 13 · 2024: 14 · 2023: 18 · 2022: 25 · 2021: 32 · 2020: 31 · 2019: 32 · 2018: 43 · 2017: 33 · 2016: 30 · 2015: 42 · 2014: 27 · 2013: 29 · 2012: 29
FWCI
12.19
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of California, San Diego
  • National Institute of Mental Health (P30MH062512)
  • Center for Medicinal Cannabis Research, University of California, San Diego
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
cannabis smoking, neuropathic pain, delta-9-tetrahydrocannabinol, cannabinoid analgesia, refractory pain, pain intensity, mood, daily functioning, tolerability, opioid-refractory pain
MeSH terms
Activities of Daily Living, Adult, Affect, Double-Blind Method, Female, Humans, Male, Marijuana Smoking, Middle Aged, Pain Measurement, Intractable Pain, Pain, Intractable, Placebos, Plants, Medicinal, Polyneuropathies, Dronabinol, HIV Infections, Cross-Over Studies, Analgesics, Non-Narcotic

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