Analgesic Efficacy of Smoked Cannabis

INVESTIGATOR: Mark Wallace, M.D.

STUDY LOCATION: University of California, San Diego

PROJECT TITLE: Analgesic Efficacy of Smoked Cannabis

PROJECT TYPE: Clinical Study

STATUS: COMPLETE

RESULTS:

In a randomized, double-blinded, placebo controlled, crossover trial in fifteen healthy volunteers, we evaluated the effects of low, medium, and high dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannibinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 minutes after drug exposure and pain, hyperalgesia, tetrahydrocannibinol plasma levels, and side effects were assessed.

Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 minutes after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannibinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests.

This study suggests that there is a window of modest analgesia for smoked cannabis with lower doses decreasing pain and higher doses increasing pain.

The full results of this study were published in the journal Anesthesiology.

ABSTRACT:

By every criteria (deterioration in quality of life; loss of work days, and therapy directed dollars) pain is appreciated to be a major medical problem. Recent findings in the molecular biology and the pharmacology of pain transmission have shed light on mechanisms of nociceptive processing and the activity of a variety of "novel therapeutic" modalities that include the cannabinoids. Although the pre-clinical literature suggests that the cannabinoids produce antinociception and anti-hyperalgesic effects, the efficacy of the cannabinoids in the human pain state is unclear. As an experimental variable, clinical pain is a multidimensional phenomenon with few objective physical correlates. Many other factors such as emotional status and coping skills, make "pain" difficult to study in the clinical setting. An important development has been the implementation of well-controlled experimental pain models to investigate the sensory components of pain processing and to use these models in the assessment of analgesic efficacy in normal volunteers. To the degree that human experimental pain models can predict analgesic efficacy of novel agents, the role of mechanisms defined in preclinical studies can be translated to the human experience under well-controlled conditions. Human experimental pain has been used to test a wide range of currently available analgesics. Knowing the effect of these agents on human experimental pain, I now wish to study the effects of cannabis on human experimental pain and how this compares to commonly used analgesics.

PUBLICATIONS:

Type:

Title:

Journal Article Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, Gouaux B, Abramson I (November 2007) Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers. Anesthesiology. 2007 Nov;107(5):785-96.

Study to Examine Possible Effects of Cannabis Compound for Common Movement Disorder

Press Release, UC San Diego Health, September 18, 2018

Researchers at University of California School of Medicine are preparing to launch a novel clinical trial to examine the safety, efficacy and pharmacological properties of cannabis as a potential treatment for adults with essential tremor (ET). Currently, ET is treated using repurposed medications originally developed for high blood pressure or seizures. Surgery is another option.

Scheduled for early 2019, the phase I/II trial will assess efficacy and tolerability of an oral cannabis formulation comprised of cannabidiol (CBD) and low-dose tetrahydrocannabinol (THC). Researchers say it will be the first time this combination has been studied for treatment of ET.

“This study will provide key insights,” said Fatta Nahab, MD, neurologist at UC San Diego Health and associate professor of neurosciences at UC San Diego School of Medicine. “If found to be safe and effective, cannabis would not only serve as an exciting new addition to the limited treatment options currently available for patients with ET, but it might also provide scientists with new insights on essential tremor.”

Read the full press release here


Cannabis for Chronic Nerve Pain: Mechanism Revealed?

Damian McNamara, Medscape, September 7, 2018

New imaging findings show how tetrahydrocannabinol (THC), the psychoactive component of cannabis, works in the brain to effectively treat chronic neuropathic pain.

Results of a small randomized, double-blind, crossover trial show that THC-induced pain relief was associated with reduced functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex.

"The main message of this paper is that THC, the psychoactive component in cannabis, does seem to exert a beneficial effect on proven chronic nerve pain.

This effect seems to involve a breakdown in functional connectivity between brain regions that process different dimensions that construct the experience of pain," study author Haggai Sharon, MD, who leads the Consciousness & Psychopharmacology research team at Sagol Brain Institute, Tel Aviv, Israel, told Medscape Medical News.

Read the article here


Cannabis Compound May Help Reduce Symptoms of Psychosis

Bob Curley, Healthline, September 5, 2018

Chronic marijuana use has been linked to increased risk of psychiatric problems. There’s even a name for the condition — cannabis-induced psychosis (CIP).

A new study, however, shows that a nonpsychoactive compound found in cannabis seems to reduce abnormal brain functions associated with psychosis, which includes diseases such as schizophrenia and bipolar disorder.

Researchers at King’s College London report in the journal JAMA Psychiatry that a single dose of cannabidiol (CBD) could someday be an effective alternative to the antipsychotic drugs in use since the 1950s.

These include Thorazine and Haldol, which have limited effectiveness and can cause serious side effects.

“It’s clear that the existing drugs have provided a lot of patients with schizophrenia the ability to function in society, but they’re not a cure,” Dr. Igor Grant, chair of the department of psychiatry at the University of California at San Diego School of Medicine and director of the school’s Center for Medicinal Cannabis Research, told Healthline.

Read the story here


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