Cannabis as a source of medicines
Submitting InstitutionUniversity of Aberdeen
Unit of AssessmentBiological Sciences
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Neurosciences, Pharmacology and Pharmaceutical Sciences
Summary of the impact
Research at the University of Aberdeen has directly contributed to the
development of the cannabis-based medicine, Sativex®, which was licensed
in the UK in 2010 for relieving neuropathic pain and spasticity of
multiple sclerosis (MS), removing the need for patients to self-medicate
with illegal, "unregulated" cannabis. The research has both enhanced
patient welfare and promoted collaboration with industry. Several other
countries have also approved Sativex®. Apart from such direct benefits,
the research has also increased understanding of the benefits of
cannabis-based medicines among the general public, and the main researcher
has advised the Home Office on pertinent legislation. Therefore the
claimed impact here includes benefits to health and welfare guidelines
and on the public understanding of science. In addition industry has
invested in research and development and a new product has been
Mechoulam, Pertwee and others discovered in the early 1990s the
endocannabinoid family of natural substances produced by the body which
have actions similar to those of the psychoactive ingredient in cannabis.
Since then Pertwee's research, as Professor of Neuropharmacology at the
University of Aberdeen, has led him to be a world leader in the study of
the pharmacology and therapeutic potential of cannabinoids. Pertwee's
research was essential for the development of the drug Sativex® by GW
Pharmaceuticals which is used as a medicine in Canada and EU for
spasticity and pain in multiple sclerosis.
Pertwee instigated the first survey of cannabis users which revealed its
effectiveness to reduce MS spasticity and pain. In the 1980s and early
1990s, numerous reports appeared in the media about claimed benefits of
self-medication with cannabis for relieving symptoms of MS, but these
reports were not supported by empirical science. This prompted Pertwee, in
collaboration with Dr Paul Consroe, University of Arizona and Dr Rik
Musty, University of Vermont, to devise a questionnaire sent out in 1995
to known individuals (identified by the Alliance for Cannabis
Therapeutics) who self-medicated with cannabis. The replies received
indicated that cannabis was regarded as being particularly effective
against MS spasticity and pain . The survey results provided impetus
for the case for performing large controlled trials with cannabinoids for
these MS symptoms.
Pertwee also provided the cannabinoid pharmacological expertise that
showed the effectiveness of cannabinoids in animal models of MS. Lorna
Layward of the MS Society brought together scientists with cannabinoid
expertise (Pertwee) and MS expertise (David Baker, Professor of
Neuroimmunology at The Blizard Institute, University of London) to perform
the basic research necessary to demonstrate the effectiveness of
cannabinoids in treating MS symptoms. Their collaboration in 1998 yielded
data showing that cannabinoid receptor agonists can ameliorate spasm,
spasticity and tremor in the chronic relapsing experimental allergic
encephalomyelitis mouse model of MS. These findings led to a key paper on
the scientific rationale for treating MS with cannabinoids . Also,
importantly, this paper provided a route to evaluate more selective
cannabinoids in the future.
Pertwee's research, as Director of Pharmacology for GW, provided
essential pharmacological characterisation of the two major cannabinoid
components of the drug Sativex which underpinned its development and
helped inform the company's clinical research in development of this drug
(review  references over 30 of Pertwee's papers in this area). In
addition, Pertwee was a major academic contributor to the licencing
document produced by GW Pharmaceuticals for Sativex.
In research that will lead to new uses of cannabinoid based drugs,
Pertwee's research then led to the discovery both of the first
water-soluble cannabinoid (O-1057) (2000), and of a CB1 receptor
allosteric site (2005) (in collaboration with the Dutch pharmaceutical
company, Organon); contributed to the first pharmacological
characterisation of synthetic cannabinoids widely used as pharmacological
tools; and to the discovery of important potential therapeutic
applications for phytocannabinoids [4 to 6]. An important result of
Pertwee's research has been the demonstration that cannabinoids can be
drugs of medical benefit. Prior to this research the therapeutic potential
of cannabis was viewed with extreme caution by drug agencies and
governments because of adverse media coverage. The reputation of Pertwee's
research, demonstrating the protective role of the endogenous cannabinoid
system in serious disorders such as MS, has given the cannabinoid research
field new respectability. Key to this is Pertwee's research standing,
which has been recognized in his status as an ISI Highly Cited Researcher,
his major standing on multiple cannabinoid societies and advisory boards
and his 2011 award of the Wellcome Gold Medal by the British
Pharmacological Society "for outstanding contributions to pharmacology,
based mainly on research achievements".
References to the research
 Consroe P, Musty R, Rein J, Tillery W, Pertwee R (1997). The
perceived effects of smoked cannabis on patients with multiple sclerosis.
European Neurology 38: 44-48. First survey of the benefits of
self-medicating with cannabis claimed by multiple sclerosis patients;
the UK part of this survey was made possible by a link that Pertwee had
set up with Clare Hodges of the Alliance of Cannabis Therapeutics (ACT
 Baker, D., Pryce, G., Croxford, J.L., Brown, P., Pertwee, R.G.,
Huffman, J.W. and Layward, L. (2000). Cannabinoids control spasticity and
tremor in a multiple sclerosis model. Nature 404: 84-87. Paper
presenting the first evidence (from experiments with mice performed at
University College, London) that cannabis ameliorates multiple sclerosis
(MS) in a highly specific manner that involves the activation of
cannabinoid receptors; this project was set up by Lorna Layward of the
MS Society who brought together scientists with MS expertise (David
Baker) and cannabinoid expertise (Pertwee).
 Pertwee R.G. (2008) The diverse CB1 and CB2 receptor pharmacology of
three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and
delta9-tetrahydrocannabivarin. Br J Pharmacol. 153:199-215. This
review provides an extensive summary of the science of the plant
cannabinoids and references over 30 papers to which Pertwee contributed
and which describe cannabinoid pharmacology.
 Thomas, A., Stevenson, L.A., Wease, K.N., Price, M.R., Baillie, G.,
Ross, R.A. and Pertwee, R.G. (2005). Evidence that the plant cannabinoid
Δ9-tetrahydrocannabivarin is a cannabinoid CB1
and CB2 receptor antagonist. Br. J. Pharmacol. 146: 917-926.
The discovery in Aberdeen that the plant cannabinoid, Δ9-tetrahydrocannabivarin
(co-discovered by Pertwee in 1970; Nature 228 134-136), is a cannabinoid
CB1 receptor antagonist, has opened up
potential therapeutic uses for this compound.
 Bolognini, D., Costa, B., Maione, S., Comelli, F., Marini, P., Di
Marzo, V., Parolaro, D., Ross, R.A., Gauson, L.A., Cascio, M.G. and
Pertwee, R.G (2010). The plant cannabinoid Δ9-tetrahydrocannabivarin
can decrease signs of inflammation and inflammatory pain in mice. British
Journal of Pharmacology. 160: 677-687. Paper providing the first
in vitro and in vivo evidence that whereas the plant cannabinoid, Δ9-tetrahydrocannabivarin,
blocks cannabinoid CB1 receptors, it can
activate cannabinoid CB2 receptor and hence,
because of these two actions, has a number of important potential
therapeutic uses (e.g. for Parkinson's disease, stroke, chronic liver
diseases and cocaine dependence).
 Cascio, M.G., Gauson, L.A. Stevenson, L.A., Ross, R.A. and Pertwee,
R.G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly
potent f0612-adrenoceptor agonist and moderately potent 5HT1A
receptor antagonist. Br. J. Pharmacol. 159:129-141. Paper
presenting the first evidence that the plant cannabinoid, cannabigerol,
is a potent α2-adrenoceptor agonist and also a
5-HT1A receptor antagonist, findings that
prompted collaborative research that has recently shown that
cannabigerol acts in vivo to produce α2-adrenoceptor-mediated
signs of pain relief in mice and also amelioration of negative signs of
schizophrenia in rats.
Relevant grant funding:
£6M grant funding awarded to Roger Pertwee since 1992 for work on the
pharmacology of cannabinoids. Main funding sources have been the Wellcome
Trust, MRC (Cannabinoid Co-operative Group), BBSRC, US National Institutes
of Health and GW Pharmaceuticals.
Details of the impact
Patient health and welfare: The study of cannabinoid pharmacology
performed by Pertwee and others led to the British company, GW
Pharmaceuticals, developing the cannabis-based medicine, Sativex®.
Pertwee's research was invaluable as stated by the chairman of GW
Pharmaceuticals, Dr Geoffrey Guy, "He has played a pivotal role in
cannabinoid science, which has led to GW's development of Sativex®, the
world's first cannabis based medicine..." [a]. In 2013 Pertwee received
the International Association for Cannabinoid Medicines special award "for
his major contributions to the re-introduction of cannabis as a medicine".
Sativex® is an oromucosal spray which reduces suffering and increases the
quality of life of MS patients and removes any need to self-medicate with
cannabis obtained illegally. Internationally, Sativex® has been approved
as a treatment for spasticity and pain caused by MS in 20 countries, in
eight of which commercialisation has now commenced. GW Pharmaceuticals is
awaiting product licences in two further countries (Italy and Ireland)
that have recommended approval. Regulatory applications have also been
submitted in Switzerland and seven countries in the Middle East. In the
US, phase III clinical trials for treatment of pain in cancer patients are
Sativex was licensed in the UK in 2010. Pertwee's earlier input to the
House of Lords Select Committee on Science and Technology [b] helped
progress the legal issues hitherto slowing the development of
cannabis-based medicines and therefore allow its 2010 licensing. One UK
Sativex® user who used to self-medicate with cannabis and blogs about the
benefits of the new treatment is Sarah Martin [c]. At Pertwee's suggestion
(2011), she became UK "Patient Representative" of the International
Association for Cannabinoid Medicines.
A colleague of Pertwee's, Dr William Notcutt, Consultant in Anaesthesia
and Pain Management at James Paget University Hospital, Norfolk [d], and
who treats patients with Sativex, testifies to the significance of Sativex
in improving the quality of life of patients and carers:
"Sativex has been shown to have significant effects on symptoms such
as spasticity, muscle spasms, sleep disturbance, pain, bladder
dysfunction and quality of life for about 50% of patients who are poorly
responsive to other therapies. The improvements with Sativex can be
substantial for the patient in improving mobility, spasm and spasticity,
pain and sleep. For the carers, ...any improvement on mobility is a
help. 50% of carers/spouses also have a substantial reduction in sleep
Collaborations with industry: Pertwee has been Director of
Pharmacology for GW Pharmaceuticals since 2002 [a] having previously had
formal cannabinoid-related links with other pharmaceutical companies (e.g.
Pfizer and Organon). In addition to his own research on cannabinoid
pharmacology, Pertwee has established collaborative links with research
groups around the world to study the therapeutic properties of
cannabinoids. This ongoing partnership between the University of Aberdeen
and industry has enabled the discovery and development of other
cannabis-based medicines with important new therapeutic applications, such
as treating obesity, treating Parkinson's Disease and for suppressing
nausea/vomiting in patients undergoing chemotherapy.
Public engagement: The underpinning research and development of
Sativex has contributed to the public debate on cannabis [e] and has been
discussed by Pertwee at the British Science Association's Festivals of
Science, which are organized for the general public. His presentations at
these events at Trinity College Dublin in 2005, Aston University,
Birmingham, in 2010 and Aberdeen in 2012 attracted audiences of around 100
members of the public.
In addition, Pertwee was a major invited contributor to a Wellcome
Witnesses to Twentieth Century Medicine seminar entitled "The
Medicalization of Cannabis", which took place in London in March 2009 [e].
The audience was comprised of medical staff, clinicians, pharmaceutical
companies and MS patients. He also gave an invited talk on cannabinoids to
the general public in London at a Royal Institution event run in
association with the University of the Third Age (March 2011). This too
attracted an audience of at least 100.
This work contributed to raising awareness and understanding of cannabis
as a source of medicines in many media interviews, including BBC Radio 4's
science discussion programme The Material World (August
2008); Radio 4's Today programme (September 2010, around 7 million
listeners); and BBC Breakfast TV (September 2010).
Impacts on policy and legislation: In 2009, Pertwee was requested
by the Home Office, on behalf of the Advisory Committee on the Misuse of
Drugs, to provide advice about how best to define cannabinoid receptor
agonists in a manner that would facilitate future UK cannabis/cannabinoid
In 2011 Pertwee influenced Canadian healthcare guidelines by assisting in
the composition of Health Canada's "Information for Health Care
Professionals-Marihuana" document, providing pharmacological information
and identifying new potential therapeutic uses for cannabinoids [f].
Cannabinoid patent co-inventor: Pertwee is a named inventor of six
GW Pharmaceuticals patents and two University patents. The former are
directly linked to the development of new cannabis-based medicines
("beyond" Sativex®) [g].
Therefore the claimed impact as defined by REF is that: the quality of
life of individuals has been enhanced and well-being improved.
Healthcare guidelines have been influenced by research. Public
understanding of the subject has improved. Industry has invested in
research and development and a new product has been commercialised.
Sources to corroborate the impact
[a] GW Pharmaceuticals: summary of Pertwee's GW impact as seen in
the following GW web page with a press release about Pertwee relating to
his award from the British Pharmacological Society of the 2011 Wellcome
Gold Medal "for outstanding contributions to pharmacology, based mainly on
research achievements", and with quote from Dr. Geoffrey Guy, see:
[b] House of Lords Select Committee on Science and Technology:
House of Lords Select Committee on Science and Technology (1998) Cannabis:
The Scientific and Medical Evidence: Evidence, HL Paper 151-1. London: The
Stationery Office (ISBN 0 10 479298 1); Pertwee's input (e.g. pp.
64-83 & p. 280) added weight to arguments to allow the development
of cannabis-based medicines (see pp. 64-83 & p. 280). For a summary
[c] Multiple Sclerosis patient who has greatly benefited from taking
Sativex and through Pertwee was a UK "Patient Representative" (see
[d] Consultant providing support for the efficacy of Sativex for
Contact details: James Paget University Hospital, Great Yarmouth, UK.
[e] Wellcome Witnesses to Twentieth Century Medicine: Together
with many of those who contributed to the "medicalization" of cannabis,
Pertwee was a major invited contributor to a Wellcome Witnesses to
Twentieth Century Medicine seminar entitled "The Medicalization of
Cannabis". This Witness Seminar took place in London in March 2009. A book
from this, "The Medicalization of Cannabis" supports Pertwee's impact on
the medicalization of cannabis.
[f] Information for Health Care Professionals-Marihuana document:
[g] Patents: Pertwee is a named inventor on the following
(1) New pharmaceutical formulation comprising cannabidiol and
tetrahydrocannabidivarin; (2) Use of tetrahydrocannabinol and/or
cannabidiol for the treatment of inflammatory bowel disease; (3)
Therapeutic uses of cannabigerol; (4) New use for cannabinoid; (5) Use for
cannabinoid; (6) New cannabinoid application; (7) Sulfonamide cannabinoid
agonists and antagonists.