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Peter Reynolds

The life and times of Peter Reynolds

Posts Tagged ‘tincture

Cannabis Embarrassment At The Home Office

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The re-scheduling of Sativex, the cannabis tincture marketed by GW Pharmaceuticals is causing huge embarrassment at the Home  Office.

Everybody’s been able to go along with the white lie up to now that Sativex is some sort of highly complex, super scientific, super medicine containing cannabinoids. True enough, GW Pharma has put millions into development and testing in order to jump through the hoops the government has demanded.  At the end of the day though, all Sativex consists of is a tincture, an alcohol extract of herbal cannabis.  It’s made simply by gently heating a blend of herbal cannabis in ethanol and then adding a little peppermint oil to taste.

An Honourable Man?

The Medicines and Healthcare Products Regulatory Agency (MHRA) has approved Sativex for the treatment of muscle spasticity in MS.  I understand that an approval for the treatment of cancer pain is expected shortly.  The problem for the Home Office is that Sativex now has to be re-scheduled under the Misuse of Drugs Act 1971.   Cannabis is presently in schedule one as having no medicinal value.  The Advisory Council on the Misuse of  Drugs (ACMD) has recommended this week that Sativex be in schedule four, alongside  a variety of minor tranquilisers.  However, as the ACMD says, “it will not be appropriate to refer to “Sativex”, which is a proprietary name, in any amendment to the misuse of drugs regulations, and that a suitable description of the relevant component(s) of “Sativex” will have to be scheduled.”

This is going to be tough for James Brokenshire to face up to.  GW specifies that Sativex contains approximately equal proportions of THC and CBD but that’s not the whole truth.  It also contains as many as 400 other chemical compounds which occur naturally in the plant including at least 85 cannabinoids (nobody is exactly sure how many cannabinoids there are or their effects).  You see there’s not really any other accurate way of describing Sativex except to call it cannabis.  So how can Mr Brokenshire possibly move it to schedule four?  He endlessly repeats the propaganda that “there are no medicinal benefits in cannabis”.

Either Mr Brokenshire has to come clean and accept that his past position was incorrect or he has to promote some further deception.

I trust he will prove to be an honourable man.

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Cannabis And Cannabinoids: Pharmacology, Medicalization And Recreational Use

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Reproduced from Pharmacology Matters,
the Newsletter of the British Pharmacological Society
Volume 3 Issue 2, December 2010

By Professor Roger Pertwee

Discovery of Δ9-tetrahydrocannabinol

Cannabis has been used as a medicine, for religious ceremonies and recreationally for over 5000 years. Indeed, an alcohol-containing tincture of cannabis (Figure 1) was a licensed medicine in the UK until its withdrawal in the early 1970’s.

In contrast, the discovery that cannabis contains (–)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and that many of the effects experienced when cannabis is taken recreationally are caused by this ‘phytocannabinoid’ was made less than 100 years ago (Pertwee, 2006). These effects include altered mood (usually euphoria); altered perception such that colours seem brighter, music more pleasant and ‘felt time’ appears to pass more slowly than ‘clock time’; an increased desire for sweet food (the ‘munchies’); changes in thought processes; impaired memory…and eventual drowsiness. They can also include increased heart rate, a lowering of blood pressure resulting in dizziness and, at high doses, hallucinations and feelings of paranoia. There is good evidence too that Δ9-THC targets the reward centres of the brain in a manner that can lead to psychological dependence, and that abrupt termination of repeated use of cannabis or Δ9-THC can trigger a transient physical withdrawal syndrome that in abstaining recreational cannabis users most commonly includes disturbed sleep, reduced appetite, restlessness, irritability, sweating, chills, a feverish feeling and nausea.

Some Cannabinoid Pharmacology

The discovery of Δ9-THC was followed by the development of synthetic compounds capable of inducing Δ9-THC-like effects. Results obtained from pharmacological research with some of these compounds culminated in the discovery that they produce many of their central effects by activating specific sites on nerve terminals called cannabinoid CB1 receptors in a manner that influences the normal functioning of the brain (Pertwee, 2006). This finding prompted a search for molecules within our own bodies that can activate these receptors and, in 1992, led to a second major discovery – that we do indeed produce and release such molecules. The first of these ‘endocannabinoids’ to be identified was an ethanolamide of the omega-6 unsaturated fatty acid, arachidonic acid. It was named
‘anandamide’, ananda being the Sanskrit word for internal bliss. It has subsequently emerged that there is at least one other cannabinoid receptor (CB2), that there are other endocannabinoids, and that this ‘endocannabinoid system’ of receptors and endogenous receptor activators plays major roles in the control of our health and in ameliorating unwanted symptoms such as pain.

The search is now on for additional cannabinoid receptors and endocannabinoids. Indeed, we have obtained evidence that ethanolamides, which are converted in our bodies from omega-3 polyunsaturated fatty acids that are found, for example, in fish oil, can both activate cannabinoid receptors and attack cancer cells (Brown et al., 2010).

The Medicalization Of Cannabinoids

Fig. 1. Tincture Of Cannabis

Individual cannabinoids first entered the clinic in the 1980’s (Crowther et al., 2010). The first of these was Nabilone (Cesamet), a synthetic Δ9-THC-like compound that is used to suppress nausea and vomiting produced by cancer chemotherapy. Synthetic Δ9-THC (Marinol) was licensed soon after Nabilone for the same purpose, and subsequently as an appetite stimulant, particularly for AIDS patients. Nabilone
and Marinol were recently joined in the clinic by Sativex: in Canada (2005) for the relief of multiple sclerosis and cancer pain and in the UK (2010) to treat spasticity due to multiple sclerosis. Sativex has also received regulatory authorisation in Spain. Its main constituents are two phytocannabinoids, Δ9-THC and cannabidiol, both extracted from cannabis.

Importantly, whereas exogenously administered cannabis and individual cannabinoids such as Δ9-THC and Nabilone target all cannabinoid receptors in the body and so ‘flood’ the whole endocannabinoid system, endocannabinoids released endogenously are somewhat more selective since they seem to be released in a manner that only targets subpopulations of their receptors. Although such release is often ‘autoprotective’ it can sometimes be ‘autoimpairing’, leading for example to CB1 receptor-mediated obesity. There is, however, currently little interest in developing medicines from compounds that block CB1 receptors, as such a blockade could well also suppress CB1 receptor-mediated autoprotection. Indeed, the CB1 receptor blocking drug, Rimonabant, was recently withdrawn from the clinic because of an increased incidence of depression and suicidality in patients taking it as an anti-obesity agent.

The fact that Cesamet, Marinol and Sativex are all in the clinic is of course an indication that, as prescribed, these medicines do significantly more good than harm. Even so, there is considerable interest in developing a second generation of cannabinoid medicines that display even greater ‘benefit-torisk ratios’ (Pertwee, 2009). Possibilities include compounds that avoid the production of unwanted cannabinoid CB1 receptor-mediated effects by:

(1) Only activating cannabinoid receptors that are located outside the brain and spinal cord.

(2) Only activating cannabinoid receptors in particular tissues such as skin or spinal cord by being administered directly into these tissues.

(3) Activating cannabinoid CB2 but not cannabinoid CB1 receptors.

(4) Being administered at low doses that produce a cannabinoid receptor-mediated enhancement of the sought after effects of  non-cannabinoid medicines but are insufficient to produce significant cannabinoid receptor-mediated unwanted side effects.

(5) Boosting the levels of endocannabinoids when these are being released in an ‘autoprotective’ manner, for example to relieve pain.

(6) Targeting ‘allosteric’ sites that we have discovered to be present on cannabinoid CB1 receptors in a manner that will boost the ability of autoprotectively released endocannabinoids to activate these receptors.

Cannabis: A Complex Scenario

Δ9-THC is synthesized in the cannabis plant from a nonpsychoactive precursor, Δ9-THC acid. This process can be greatly accelerated by heat which is why cannabis is usually smoked, often with tobacco, consumed in preheated food or inhaled from ‘volcano’ vaporizers that create fumes by heating cannabis without burning it or producing smoke. Other pharmacologically active phytocannabinoids can also be
formed from their acids by heating cannabis. These include the non-psychoactive yet pharmacologically active compounds, cannabidiol (CBD), Δ9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG), each of which has actual (CBD) or potential medical applications. Some of these phytocannabinoids are really ‘fighto’ cannabinoids, their presence in cannabis making it a pharmacological ‘battlefield’. Thus
we have discovered that although CB1 receptors are activated by Δ9-THC, they can be blocked by Δ9-THCV. It has also been found that CBD can oppose certain effects produced by cannabis or Δ9-THC. Indeed, whilst there is evidence that the presence of Δ9-THC in cannabis increases the risk of developing schizophrenia for certain individuals, there is also strong evidence that cannabidiol is a potential medicine for the treatment of schizophrenia. A further complication is that the relative concentrations of different phytocannabinoids are not the same in all strains of cannabis, in all parts of the same cannabis plant or in male and femalecannabis plants, the female flowering heads of sinsemilla (‘without seeds’) being particularly rich in Δ9-THC. This may have important consequences for those who take cannabis either recreationally or for the quite different purpose of self-medication, as high CBD:THC or THCV:THC ratios may lessen the risk from cannabis of developing schizophrenia or cannabis dependence…although probably also alter the perceived nature of a cannabis-induced ‘high’.

Spice

One notable recent event has been the arrival in the recreational cannabis world of herbal mixtures laced with synthetic cannabinoids (‘designer drugs’) such as JWH-018 (e.g. Spice or K2, named after the second highest mountain on earth). These little-investigated synthetic cannabinoids share the ability of Δ9-THC to activate cannabinoid CB1 receptors and hence to produce a ‘high’. Moreover, any of them that
activate these receptors more strongly than Δ9-THC will most likely produce a more intense ‘high’ and perhaps also more serious unwanted effects than usually experienced by recreational cannabis users. They probably also differ from THC in other ways. Thus, although Δ9-THC shares its ability to target cannabinoid receptors with many synthetic compounds, the additional pharmacological actions it possesses provide it  with a unique ‘pharmacological fingerprint’ that distinguishes it from many of these other compounds.

Harm Minimization For Recreational Cannabis

One important challenge for the International Narcotics Control Board that monitors and implements United Nations drug control conventions is to select an optimal but workable strategy for minimizing the harm that is now being caused both to themselves and to Society by some of the many  millions of people world-wide who currently take cannabis (or Spice) recreationally and also, indeed, by some of those who self-medicate with ‘street’ cannabis. For the UK, options include leaving the present law unchanged and increasing or
decreasing current penalties for the supply and/or possession of ‘street’ cannabis. It would also be advisable to develop strategies directed (i) at discouraging cannabis from being taken by adolescents or other individuals who are thought to be at particular risk from cannabis-induced harm and (ii) at providing advice (a) about combinations and levels of cannabinoids in cannabis that are thought to be the least
harmful and (b) about how to take cannabis as an inhaled unburnt vapour or in other ways that avoid the lung damage caused by smoked cannabis. It will be important that policy makers have discussions with cannabinoid pharmacologists whilst considering these and any other potential strategies for minimizing the harm caused by recreational cannabis.

References
Brown I, Cascio MG, Wahle KWJ, Smoum R, Mechoulam R, Ross RA, Pertwee RG and Heys SD. Cannabinoid receptor dependent and independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor positive and negative prostate cancer cell lines.
Carcinogenesis 2010; 31: 1584-1591.
Crowther, SM, Reynolds, LA and Tansey, EM (eds). The Medicalization of Cannabis. Witness Seminar Transcript. Volume 40. The Wellcome Trust Centre for the History of Medicine, at UCL. 2010; http://www.ucl.ac.uk/histmed/downloads/c20th_group
Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 2006; 147: S163-S171.
Pertwee RG. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 2009; 156: 397-411.
Professor Roger Pertwee has three degrees from the University of Oxford: MA (in biochemistry), D.Phil. (in pharmacology) and D.Sc. (in physiological sciences). He is Professor of Neuropharmacology at the University of Aberdeen, Director of Pharmacology for GW Pharmaceuticals, co-chairman of the International Union of Pharmacology (IUPHAR) Subcommittee on Cannabinoid Receptors, a co-ordinator of the British Pharmacological Society’s Special Interest Group on Cannabinoids and visiting Professor at the University of Hertfordshire. He has also served as chairman of the International Association for Cannabis as Medicine (IACM; 2005-2007) and as President of the International Cannabinoid Research Society (ICRS; 2007-2008; 1997-1998) and is currently ICRS International Secretary and a member of the IACM board of directors. He was the recipient of the 2002 Mechoulam Award “for his outstanding contributions to cannabinoid research” and in 2005 was recognized to be an “ISI Highly Cited Researcher” and hence among “the world’s most cited and influential researchers” (see Pertwee at http://isihighlycited.com/). His research has focused mainly on the pharmacology of  cannabinoids. This he began in 1968 at Oxford University and continued when he moved to Aberdeen in 1974. His research has played major roles in:
• the discovery of endocannabinoids and the endocannabinoid system;
• the recent discovery that ethanolamides formed from omega-3 polyunsaturated fatty acids seem to be endocannabinoids;
• the gathering of evidence supporting cannabinoids for the management of multiple sclerosis;
• the discovery that tetrahydrocannabivarin (THCV) is a phytocannabinoid;
• the pharmacological characterization of certain phytocannabinoids and of novel synthetic cannabinoids, e.g. the phytocannabinoids THCV, cannabidiol and cannabigerol, the first water-soluble cannabinoid (O-1057), the first CB1 receptorselective agonists (e.g. methanandamide), and a widely-used CB2 receptor antagonist (AM630);
• the discovery of a cannabinoid CB1 receptor allosteric site;
• the development of cannabinoid bioassays, some widely used (e.g. the “ring test”).
See also www.abdn.ac.uk/ims/staff/details.php?id=rgp

European Parliament – Public Hearing On Cannabis Regulation

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The European Coalition for Just and Effective Drug Policies (ENCOD) has organised a public hearing on cannabis regulation at the European Parliament on 8th December 2010.  See here for full details.

In March 2009, the European Commission published the “Report on Global Illicit Drug Markets 1998 – 2007” .  This concludes that current policies of prohibition are failing in their main objective to reduce the demand and supply of illicit drugs.  Current policies may also be a crucial factor in generating and increasing harm to individual drug users, their direct surroundings and society at large.

According to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in its 2010 annual report, Europe faces new challenges posed by changes in drug supply and use.  The report also highlights the increased usage of cocaine, heroin and of a record number of new synthetic drugs.

ENCOD says that prohibitionist policies have failed to tackle the issues of drugs and drug use effectively and it is time to investigate alternative approaches.  European authorities must produce a thorough impact assessment of the costs of the current policy of prohibition and the economic benefits of decriminalisation and, as a start, the regulation of the cannabis market.

Victor Hamilton

It has been calculated that cannabis regulation would save billions in law enforcement costs, foster harm reduction, weaken the illegal cartels, and provide the opportunity to generate considerable income from taxes. The examples of California, Spain, The Netherlands and Portugal lead the way.

Victor Hamilton, the well known cannabis campaigner and former Legalise Cannabis Alliance (LCA) parliamentary candidate, liaises as a UK representative with ENCOD.   He has submitted the following letter to ENCOD in advance of the public hearing on the current state of cannabis in Britain.

Dear Joep,
Thank you for the invitation to attend the hearing on 8th December 2010.  I am afraid that both my health and the expense involved prevent me from attending.

However, as you know, ending the prohibition of cannabis and encouraging more and better use of the plant in all its forms is my main concern.  Cannabis offers many benefits medicinally, recreationally, spiritually and, as hemp, in ecologically sound fuel, construction materials, paper and plastics alternatives.  Prohibition of cannabis is a far greater crime than any perpetrated by those who use it.  It is a scandal and a sad litany of wasted opportunity and resources.

In the UK, based on research I have done and confirmed by the Independent Drug Monitoring Unit (IDMU), a legalise, regulate and tax regime could produce between £4 – 6 billion pa in new tax revenue.

For the benefit of the hearing, please allow me to update you on the present situation in Britain.

Calls For Decriminalisation

There have been calls for a relaxation of cannabis laws from a number of sources:  The Bar Council, the British Medical Association, the Royal College of Physicians, The Lancet, Professor Roger Pertwee, Professor David Nutt and the Association of Chief Police Officers.  The new coalition government’s “Your Freedom” website was swamped with calls for legalisation.

Reaction To Propositon 19

The cannabis community was eager with anticipation for the Proposition 19 vote in California, despite a dearth of media attention.  Even the BBC, obliged under its charter to provide balanced coverage, found very little time for an issue that affects at least six million Britons.  Strangely, the best of the lot was The Daily Telegraph, formerly known as the most conservative paper, it told us more about what was happening than any of the others.

The result was a disappointment and reminded us how our own campaigning has suffered from internal divisions and a lack of focus.  Nevertheless. legalisation seems inevitable in the US, even if only at state level, within the next few years.

Formation of British Medicinal Cannabis Register

This exciting initiative to create a database of medicinal users in Britain was announced only in November.  I was honoured to be invited to sit on the BMCR council as a medicinal user representative.  Other members of the council include very eminent individuals such as Baroness Meacher, the MP Paul Flynn, Matthew Atha of IDMU and Dr Malcolm Vandenburg, the pre-eminent expert witness on drugs.

The real coup though was the announcement of Professor Leslie Iversen as a council member.  Professor Iversen is the government’s chief scientific advisor on drugs.  Yes that’s the British government which continues to state that cannabis has “no medicinal benefits”.

Subversion of Schengen Agreement

Several British medicinal users travelled to Holland for prescriptions from a doctor believing that their medicine was then protected by the Schengen Agreement.  At first the Home Office agreed but then changed its position to say that British residents are not covered.  The ridiculous situation now is that any non-UK resident can bring prescribed medicinal cannabis into Britain and use it without restriction. A UK resident cannot.

Increasing Evidence Of Medicinal Benefits

There is a never ending flow of information from all around the world on the extraordinary power of cannabis as a medicine.  Facebook groups, blogs and organisations such as the LCA and UKCIA keep spreading the news.  Particularly strong evidence has been revealed for cannabinoids as a treatment for Alzheimer’s, head, neck, breast and prostate cancer, fibromyalgia, ADHD and migraine.  The mainstream media seem only interested in scandal and scare stories. They publish news about vastly expensive new pharmaceutical products but not about cannabis cures.

Confusion At The Home Office

Understandably, the British government’s position looks increasingly absurd.  The Home Office veers between describing cannabis as very harmful, harmful, dangerous, extremely dangerous and changes its story every time it is challenged.

Approval of Sativex

Sativex won welcome approval from the medicines regulator as a treatment for spasticity in MS. Despite the fact that Sativex is nothing more than a tincture of herbal cannabis, the government now maintains that “cannabis has no medicinal benefits in herbal form”.  Sativex is approximately eight times the cost of herbal medicinal cannabis and many health authorities are refusing to fund it.

New UK Drug Strategy

The government is to announce a new drugs strategy in December.  There is expected to be a shift in emphasis towards healthcare interventions rather than criminal sanctions but no move away from prohibition.  The more liberal views expressed by both David Cameron and Nick Clegg over the last 10 years seem to have changed now they have come to power.

Joep, I hope this is helpful and informative for the hearing and for you and your colleagues.

Victor Hamilton

British Medicinal Cannabis Register

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In California there are more than 500,000 medical marijuana card holders.  How many people use cannabis as medicine in Britain?

The British Medicinal Cannabis Register aims to find out and provide a database of facts and evidence for doctors, scientists, researchers, campaigners, government and anyone with a bona fide interest.   Users register via the BMCR website, providing details of their method of use and the conditions treated.  While patient confidentiality is guaranteed and records held on the database will have the same legal status as any other medical record, users do not have to provide their full address.   They can register with the first part of their postcode and a verifiable email address.

Of course, according to the British government, “cannabis is dangerous and has no medicinal benefits”.  However, Sativex, a cannabis tincture, has been approved by the MHRA as a treatment for MS spasticity.  Sativex is pharmacologically identical to cannabis.  It is cannabis – with the addition of ethanol and a little peppermint oil. (A tincture is an alcoholic extract.)

There is no more common sense in US federal law where cannabis is a schedule 1 drug with “no medicinal uses”, yet the US government has held a patent  (no. 6630507) since 2003 for “cannabinoids as antioxidants and neuroprotectants, for example, in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”

If you can make any sense of either the British or US governments’ position then please educate me?   I think they are irrational and cruel.  They actively deny people in pain and suffering the relief they need which is comprehensively proven both by science and experience.  On both sides of the Atlantic this amounts to nothing less than an evil injustice and oppression of vulnerable people.

Thank God and the US constitution that in America 14 states have introduced a regulated system of medical marijuana.  Two-thirds of Europe permits medicinal cannabis and Israel has just introduced a major programme including new growing facilities and dispensaries.  In Britain there is no such compassion and the Home Office ducks and dives and manipulates and dissembles to evade EU law that would permit cannabis as medicine.  In the UK there is appalling wickedness and cruelty perpetrated on the back of political cowardice.

Baroness Meacher

The BMCR was launched this week and received an immediate boost with the announcement of Baroness Molly Meacher, Paul Flynn MP,  Matthew Atha and Dr Michael Vandenburg as members of its governing council.  Baroness Meacher has a distinguished career in health and social care.  Paul Flynn has long campaigned for drug law reform.  Matthew Atha is the director of the Independent Drug Monitoring Unit and Dr Michael Vandenburg is the pre-eminent expert witness in the courts on pharmaceuticals and drugs.

Whether the BMCR succeeds in its aims depends entirely on whether those who use cannabis as medicine have the courage to register.  Only then will sufficent evidence be available to embarrass the government into essential and overdue reform.  The danger is that those who find relief  will prefer to keep quiet and say nothing.  No one could blame them if they do.

It is time for all those concerned to grasp this nettle and make a stand. Are we seriously going to continue to imprison sick and disabled people for using a medicine that is proven to be effective and far less costly, dangerous and harmful than pharmaceutical alternatives?

I urge all those concerned to register at the BMCR website: www.bmcr.org.uk.