Nature 1998 Sep 24;395(6700):381-3  An analgesia circuit activated by cannabinoids.

Meng ID, Manning BH, Martin WJ, Fields HL

Department of Neurology, W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco 94143-0114, USA. idmeng@phy.ucsf.edu

"...Furthermore, cannabinoids produce analgesia by modulating RVM neuronal activity in a manner similar to, but pharmacologically dissociable from, that of morphine. We also show that endogenous cannabinoids tonically regulate pain thresholds in part through the modulation of RVM neuronal activity. These results show that analgesia produced by cannabinoids and opioids involves similar brainstem circuitry and that cannabinoids are indeed centrally acting analgesics with a new mechanism of action.

PMID: 9759727, UI: 98430527

Russo E

Department of Neurology, Western Montana Clinic, Missoula 58907-7609, USA. ptm5739@montana.com

Cannabis, or Marijuana, has been used for centuries for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a headache remedy by the most prominent physicians of the age between 1874 and 1942, remaining part of the Western pharmacopoeia for this indication even into the mid-twentieth
century. Current ethnobotanical and anecdotal references continue to refer to its efficacy for this malady, while biochemical studies of THC and anandamide have provided a scientific basis for such treatment. The author believes that controlled clinical trials of Cannabis in acute migraine treatment are warranted.

Publication Types:
* Historical article
* Review
* Review, tutorial

PMID: 9696453, UI: 98359642

Stella N, Schweitzer P, Piomelli D

The Neurosciences Institute, San Diego, California 92121, USA.

"Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment..."

PMID: 9285589, UI: 97429951

Consroe P, Musty R, Rein J, Tillery W, Pertwee R

Department of Pharmacology/Toxicology, University of Arizona Health Sciences Center, Tucson 85721-0207, USA. consroe@pharmacy.arizona.edu

Fifty-three UK and 59 USA people with multiple sclerosis (MS) answered anonymously the first questionnaire on cannabis use and MS. From 97 to 30% of the subjects reported cannabis improved (in descending rank order): spasticity, chronic pain of extremities, acute paroxysmal phenomenon, tremor, emotional dysfunction, anorexia weight loss, fatigue states, double vision, sexual dysfunction, bowel and bladder dysfunctions, vision dimness, dysfunctions of
walking and balance, and memory loss. The MS subjects surveyed have specific therapeutic reasons for smoking cannabis. The survey findings will aid in the design of a clinical trial of cannabis or cannabinoid administration to MS patients or to other patients with similar signs or symptoms.

PMID: 9252798, UI: 97396625

Calignano A, La Rana G, Giuffrida A, Piomelli D

Dipartimento di Farmacologia Sperimentale, Universita di Napoli, Italy.

The potent analgesic effects of cannabis-like drugs and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord indicate that endogenous cannabinoids such as anandamide may contribute to the control of pain transmission within the central nervous system (CNS). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor, exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than
does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CB2-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.

PMID: 9685157, UI: 98348318

Holdcroft A, Smith M, Jacklin A, Hodgson H, Smith B, Newton M, Evans F

Hammersmith Hospital, London, UK.

Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation. This is the first United Kingdom report of the controlled use of a standardised pharmaceutical preparation of cannabinoids in capsular form. The therapy was assessed in a patient with familial Mediterranean fever, who presented with chronic relapsing pain and inflammation of gastrointestinal origin. After determining a suitable analgesic dosage, a double-blind placebo-controlled cross-over trial was conducted using 50 mg tetrahydrocannabinol daily in five doses in the active weeks and measuring effects on parameters of inflammation and pain. Although no anti-inflammatory effects of tetrahydrocannabinol were detected during the trial, a highly significant reduction (p < 0.001) in additional analgesic requirements was achieved. Future study designs can now incorporate prescribable forms of cannabinoids but the choice of previous cannabis users only as patients has clinical limitations. Cannabis naive patients would tolerate controlled investigations but may generate medicolegal problems.

Publication Types:
* Clinical trial
* Controlled clinical trial

Comments:
* Comment in: Anaesthesia 1997 Nov;52(11):1116-7

PMID: 9165969, UI: 97308778

Evans FJ

Department of Pharmacognosy, School of Pharmacy, University of London, U.K.

A brief history of the therapeutic uses and legal problems of cannabis as well as the component cannabinoids is given. This is followed by a discussion of drug development from delta 1-tetrahydrocannabinol and its synthetic analogues. The controversy of whether the pharmacological effects are of central or peripheral
origin is included. Then, the potentials for the development of new drugs based on the cannabinoid structure for the treatment of pain, inflammation, and related conditions are outlined. It is concluded that the central activity of cannabinoids is confirmed and that the presence of a C-5 hydroxy group confers potent peripheral activity.

Publication Types:
* Review
* Review, tutorial

PMID: 1659702, UI: 92066682