Cannabinoids In Reduction of HIV Pain: Dr. Donald Abrams

The depth of research on this subject by Dr. Abrams, Professor of Medicine at UCSF School of Medicine, is intense. His research on cannabis is dated far before the term 'cannabinoid medicine' even existed. This study is on the effects of smoked cannabis for neuropathic pain that plagues those with this brutal 'king' of all auto-immune diseases. With an outcome showing a reduction of 34% with this type of chronic and very harsh pain, we see a pattern in cannabis being the answer for various ailments that cause us pain. Many with H.I.V. will end up on strong pain medications which will quickly deteriorate their bodily structure and advance the deadly virus. The authors go into depth in the full paper in regards to how the patients were not only able to reduce pain, but also medications. Cannabinoid Replacement Therapy existed long before that term did as well – and this research proves this.

Cannabis in painful HIV-associated sensory neuropathy A randomized placebo-controlled trial

D.I. Abrams, MD; C.A. Jay, MD; S.B. Shade, MPH; H. Vizoso, RN; H. Reda, BA; S. Press, BS; M.E. Kelly, MPH; M.C. Rowbotham, MD; and K.L. Petersen, MD

Abstract:

Objective: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. Methods: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving 30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. Results: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR 71, 16) vs 17% (IQR 29, 8) with placebo (p 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. Conclusion: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

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Discussion. Over a 5-day inpatient intervention period, smoking cannabis cigarettes three times a day reduced HIV-SN pain by 34%, significantly more than the 17% reduction with placebo cigarettes. A 30% reduction in pain has been validated as a clinically significant level of improvement.23 In the current study, half (52%) of those randomized to cannabis experienced at least a 30% reduction in pain, while a quarter (24%) of those randomized to placebo experienced a similar reduction in pain. In this randomized, placebo-controlled study, the number needed to treat (NNT) on the primary outcome measure of 30% pain reduction among all completing patients was 3.6 (1/[52%24%]). Trials vary in their primary outcome measure, so comparing NNT figures only approximates relative potency. The NNT for lamotrigine was 5.4 for HIV-related painful DSP.4,24 Although one group of investigators reported success with gabapentin, their data analysis does not allow calculation of an NNT.5 The NNT in the present study is comparable to that reported in trials of gabapentin for other types of chronic neuropathic pain. In a large study of gabapentin for postherpetic neuralgia the NNT was 3.4 and for diabetic neuropathy the NNT was 4.0.25,26 A recent meta-analysis of 107 controlled trials for neuropathic pain showed that only tricyclic antidepressants and higher potency opioids consistently achieved NNT values lower than 3.7.24 However, for HIV-SN, tricyclic antidepressants were not effective.9,10 Opioids have not been systematically evaluated for painful HIV-SN, but studies show efficacy across a broad spectrum of neuropathic pain disorders.27,28 In addition to patient-reported changes in ongoing chronic pain, smoked cannabis attenuated the cutaneous hyperalgesia associated with central neuronal sensitization produced by a standardized experimental pain model. Although one cannot entirely exclude pain relief due to relaxation, a high, or unblinding, the mood effects recorded argue against such an explanation. Only one of the six Profile of Mood States subscales (depression-dejection) showed a significant group difference, and actually favored placebo. Moreover, ratings of side effects in the cannabis group were low. The rigorous experimental pain model outcome measures are novel to each patient and not strongly associated with expectations of relief of chronic pain. Areas of secondary hyperalgesia are mapped by an investigator while the patient looks away, and thus may be less subjective than pain intensity ratings on a VAS scale. Therefore, the present study provides evidence that cannabis has analgesic effects on acute central neuronal sensitization produced by the experimental pain model as well as on the neuronal mechanisms associated with painful HIV-SN. The results reported here in neuropathic pain patients exposed to an experimental pain model are consistent with preclinical pain model studies with cannabinoids. Systemic cannabinoids are effective in animal models of acute mechanical and thermal pain, inflammation and hyperalgesia, and nerve injury.29-35 In healthy human volunteers, smoked cannabis increased pressure pain tolerance thresholds.36 The present study in chronic pain patients also shows an effect on experimental hyperalgesia. Although smoked cannabis did not appear to suppress the painfulness of the LTS procedure (analogous to the hot plate or tail flick test in animals), this may reflect the relatively low concentration of delta-9-THC in the study cigarettes. The clinical literature on cannabinoids for pain conditions other than HIV-SN is limited and essentially restricted to isolated delta-9-THC preparations. Fifteen and 20 mg of delta-9-THC produced significant analgesia in cancer patients with pain, as well as antiemesis and appetite stimulation, but some patients reported unwanted side effects such as sedation and depersonalization at the 20 mg dose level.37,38 In a follow-up study, 10 mg of delta-9-THC produced analgesic effects comparable to 60 mg of codeine, and 20 mg of delta-9-THC was equivalent to 120 mg of codeine. Two recent placebo-controlled studies of cannabinoids for central neuropathic pain associated with multiple sclerosis produced results similar to the present study. In a crossover trial of synthetic delta-9-THC up to 10 mg/day, an NNT of 3.5 was reported.39 A trial of a sublingual spray containing delta-9-THC alone or combined with cannabidiol showed a 41% pain reduction with active drug vs a 22% reduction with placebo.40 The Institute of Medicine report on cannabis and medicine concluded that cannabinoids likely have a natural role in pain modulation, control of movement, and memory.41 The Institute of Medicine report, along with other recent reviews, suggest that if cannabis compounds can be shown to have therapeutic value then the margin of safety is acceptable.42,43 An acceptable safety margin has been shown in the present study as well as in a previous study of cannabinoids in patients with HIV-1 infection.