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Academy of Pharmaceutical Sciences

Cannabinoids: from plant to patient

The Academy of Pharmaceutical Sciences, together with the Multiple Sclerosis Society and the British Pharmacological Society, held a one-day symposium at the Royal Pharmaceutical Society’s headquarters, London, on April 5. The meeting included presentations on basic scientific research with cannabinoids, personal experiences and the clinical use of cannabis and cannabinoids. Jo Barnes reports

Cannabis had a good pedigree as a medicine, Dr ELIZABETH WILLIAMSON (senior lecturer, centre for pharmacognosy and phytotherapy, School of Pharmacy, University of London) said. It had first been used medicinally several thousand years ago. In the United Kingdom, its use had remained legal until the Misuse of Drugs Act 1971, which prohibited all use.

Dr Williamson said that anecdotal evidence from people who used cannabis medicinally suggested that the effects of cannabis were greater than those of isolated cannabinoids, such as tetrahydrocannabinol (THC), alone. It was important to determine whether this was the case and, if so, what other cannabinoids were contributing to the effect and how they modified each other. There was already some evidence that cannabis had effects that THC alone did not. THC alone could be anxiogenic, but cannabidiol (CBD) had anxiolytic properties and modified the anxiogenic effect of THC. Furthermore, in mice, CBD increased the concentration of THC in the brain, so an interaction was occurring between these constituents.

“We need to know if a combination of constituents is necessary. If there is a single compound that works better than THC and without the psychoactive effects, that would be ideal,” Dr Williamson said. Psychoactivity was not always desirable, because most people with multiple sclerosis (MS) wanted to continue working.

In collaboration with colleagues at the Institute of Neurology, London, Dr Williamson's group had conducted studies using a mouse model of multiple sclerosis.

Presenting this work, Dr DAVID BAKER (department of neurochemistry, Institute of Neurology, University College London) said the preliminary results indicated that intravenous cannabis extract (5 mg/kg, containing THC 20 per cent) had greater antispastic effects than D-9-THC (1 mg/kg IV). There were several explanations for why cannabis could be more effective than a single, isolated cannabinoid:

Other compounds in cannabis could beneficially affect the metabolism and action of D-9-THC
Cannabis could exhibit stronger cannabinoid receptor agonism that D-9-THC alone (cannabis contained other cannabinoid receptor binding compounds, such as D-8-THC)
Compounds in cannabis could effect endogenous cannabinoids, such as anandamide, more than D-9-THC alone

Focusing on endogenous cannabinoids, Dr Baker explained that anandamide was degraded by first being taken up into cells by a transporter compound, and then broken down. If uptake into cells could be blocked, this would increase the concentration of anandamide available for binding to cannabinoid receptors. In vitro studies had shown that AM404 (a compound that blocked the anandamide transporter molecule) and cannabis extract, but not D-9-THC, inhibited SKM4-45-1, an anandamide-like synthetic cannabinoid, uptake in glioma cells.

Referring to these findings, Dr Baker said: “We already potentially have some biological explanations why cannabis could have beneficial effects over single compounds.”

Personal experience

CLARE HODGES (Alliance for Cannabis Therapeutics) gave a personal experience of MS and her use of cannabis to relieve symptoms. Ms Hodges had formed the ACT to press for cannabis to be rescheduled to Schedule 2 under the Misuse of Drugs Act. Thousands of patients were already using cannabis in a potentially dangerous way without help or supervision and were risking prosecution. For many patients, trying to obtain supplies was a big problem. Many grew their own or obtained it through networks supplying good-quality cannabis.

Patients should have some legal access to cannabis while research was going ahead — they could not wait for research, Ms Hodges said. She suggested a temporary solution would be to allow patients (whose condition was confirmed by a doctor) to grow up to six cannabis plants at home.

“We still would not know what we are taking, but it would be better than procuring cannabis from sources we did not know,” Ms Hodges concluded.

Clinical trials

Dr JOHN ZAJICEK (Derriford Hospital, Plymouth) discussed progress with the Medical Research Council funded clinical trial of oral formulations of THC and cannabis oil in patients with MS. Recruitment for the trial had started in January and was expected to continue for 12–18 months. Twenty participants were nearing week 14 of the study. The study aimed to recruit 660 patients. Details of the trial were available at www.cannabis-trial.plymouth.ac.uk.

Dr WILLIAM NOTCUTT (consultant anaesthetist, James Paget Hospital, Great Yarmouth) described a series of single patient studies in chronic pain with THC, CBD or an equal mixture delivered by sublingual spray. These had produced some encouraging results, he said.

Dr ANITA HOLDCROFT (consultant anaesthetist, Chelsea and Westminster Hospital, London) outlined the protocol for a clinical trial of oral cannabis and THC in acute post-operative pain relief. Like the MS protocol, this had been developed by the Royal Pharmaceutical Society. The trial was funded by the MRC. This study was currently recruiting researchers. Four centres would each recruit around 100 patients.

Legal situation

Professor TONY MOFFAT (chief scientist, Royal Pharmaceutical Society) summarised some of the recent developments world-wide relating to the legality of cannabis use. In Ontario, Canada, patients (with the support of their medical practitioner) could now use cannabis for medicinal purposes. Belgium had become the second European country (after the Netherlands) to decriminalise cannabis. Possession for personal use and growing of cannabis for personal use were now legal in that country. Switzerland had taken a similar approach and had also decriminalised the possession of small quantities for personal use.

In the UK, the House of Lords Select Committee on Science and Technology recommended in its 1998 report that the Government should allow doctors to prescribe cannabis for medicinal use. However, the Government had rejected this on the same day the report was published. The commitee published a second report on cannabis in March (PJ, March 31, p410).

Jo Barnes is teaching and research fellow at the centre for pharmacognosy and phytotherapy, School of Pharmacy, University of London