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July 6th, 2008, 12:49 PM
The re-emergence of the
therapeutic use of cannabis
products: recent developments
and future prospects
John Witton
The past two decades have seen renewed and concerted interest in the therapeutic
potential of cannabis. Tetrahydrocannabinol (THC), the active and most significant
constituent of cannabis, and other closely related compounds were identified in the
1960s. However, it was not until the mid-1980s and 1990s that research accelerated,
when understanding increased of the biology of the body’s endocannabinoid system
and how cannabis works on the brain. These discoveries opened up possibilities to
exploit cannabis-based products for medical use. This renewed scientific interest in the
cannabinoids is evidenced by (i) the increase in the number of research papers on the
biology of cannabinoids, from 200–300 per year through the 1970s to nearly 6 000 in
2004, and (ii) the number of cannabinoid drugs under pharmaceutical development,
rising from 2 in 1995 to 27 in 2004 (Pacher et al., 2006).
The identification of a natural cannabinoid receptor–neuromodulator system in the body
was the key to pharmacological and therapeutic developments. Receptors are the sites
of action for brain chemicals, called neurotransmitters, and often the sites of action
of drugs. Binding of the neurotransmitter or drug to the brain cell receptor causes a
response in the cell. Two cannabis receptors (termed CB1 and CB2) have been found
(Pertwee, 1997). CB1 receptors are distributed in discrete areas of the brain, particularly
concentrated in the hippocampus and cerebral cortex (areas concerned with memory
and cognition), olfactory areas, basal ganglia and cerebellum (areas concerned with
motor activity and posture control) and the spinal cord. CB2 receptors are found
peripherally and are closely linked with cells in the immune system (Kumar et al., 2001).
With the discovery of cannabis receptors it became possible to develop cannabinoid
agonists or antagonists — that is, agents that activate or bind but do not activate the
receptors — that might act as therapeutic tools or help determine the roles of the
cannabinoid receptors and the body’s own endogenous cannabinoids (British Medical
Association, 1997). Two major endocannabinoids have been identified and isolated:
anandamide and 2-arachidonoyl glycerol. This endogenous cannabinoid system is
involved in analgesia, cognition, memory, locomotor activity, appetite, vomiting and
immune control (Kumar et al., 2001).
As the structure–activity relationships of the cannabis receptors and endocannabinoid
system unfolded, the potential for cannabis-based medicines became clearer. But in a
review of these developments, a leading neuropharmacologist, Professor Leslie Iversen,
suggested that pharmaceutical companies faced a range of substantial obstacles in
developing cannabis-based medications. These obstacles were: development costs would
be high; only synthetic cannabinoids could be patented rather than the natural product;
products would be likely to be niche drugs rather than ‘blockbuster’ drugs used to treat
common health problems; there were already medicines available to treat the problems
that cannabinoids might be used for; and finally, the vast US marketplace would be
difficult to enter, with the US having strict regulatory requirements to introduce a drug
that is derived from or chemically related to a prohibited substance (Iversen, 2003).
Over the last 30 years, widely reported use of illicitly smoked cannabis for selfmedication
for a range of illnesses has brought normally law-abiding citizens into
conflict with their country’s legal system. Surveys have found that the common
indications for cannabis use include depression, multiple sclerosis, pain, migraine,
asthma and cancer-related anorexia/cachexia (Schnelle et al., 1999; Gorter et al.,
2005).
The ethical dilemmas surrounding this issue were among the factors that led to
a number of enquiries examining the therapeutic potential of cannabis products. The
British Medical Association’s 1997 report Therapeutic Uses of Cannabis and the 1998
report Cannabis: the Scientific and Medical Evidence from a Select Committee of the
House of Lords both called for the setting up of clinical trials to evaluate the potential
therapeutic use of cannabinoids. The prestigious US Institute of Medicine published
its report Medical Use of Marijuana in 1999. Together, these reports established the
evidence base to support the further examination of cannabis products for medical use.
Medical and political interest intensified in several European countries and the medical
use of cannabis was legalised in the Netherlands in 2003 (Grotenhermen and Russo,
2002; Gorter et al., 2005) and extended for a five-year period in 2007.
Naturally, cannabis products are subject to the same rigorous clinical testing and
regulatory processes as any other potential medicine. Clinical trials for new medications
normally follow three phases. In phase I the safety of the drug is established. In phase II
the efficacy of the drug is established through giving the medication to a small group of
potential patients who have the condition targeted by the medication. Finally, phase III
trials use large studies involving hundreds of patients.
(for the rest of this article....)
http://www.emcdda.europa.eu/attachements.cfm/att_53382_EN_emcdda-cannabis-mon-vol1-ch2-web.pdf
Referenced as:
This publication should be referenced as:
EMCDDA (2008), A cannabis reader: global issues and local experiences, Monograph
series 8, Volume 1, European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
References to chapters in this monograph should include, where relevant, references to the
authors of each chapter, together with a reference to the wider publication. For example:
Corrigan, D. (2008), ‘The pharmacology of cannabis: issues for understanding its use’, in:
A cannabis reader: global issues and local experiences, Monograph series 8, Volume 1,
European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
The publication is available on the Internet at:
http://www.emcdda.europa.eu/publications/monographs/cannabis
Cataloguing data can be found at the end of this publication.
Luxembourg: Office for Official Publications of the European Communities, 2008
ISBN 978-92-9168-311-6
© European Monitoring Centre for Drugs and Drug Addiction, 2008
Reproduction is authorised provided the source is acknowledged.
Printed in Belgium
Rua da Cruz de Santa Apolónia 23–25, P-1149-045 Lisbon
therapeutic use of cannabis
products: recent developments
and future prospects
John Witton
The past two decades have seen renewed and concerted interest in the therapeutic
potential of cannabis. Tetrahydrocannabinol (THC), the active and most significant
constituent of cannabis, and other closely related compounds were identified in the
1960s. However, it was not until the mid-1980s and 1990s that research accelerated,
when understanding increased of the biology of the body’s endocannabinoid system
and how cannabis works on the brain. These discoveries opened up possibilities to
exploit cannabis-based products for medical use. This renewed scientific interest in the
cannabinoids is evidenced by (i) the increase in the number of research papers on the
biology of cannabinoids, from 200–300 per year through the 1970s to nearly 6 000 in
2004, and (ii) the number of cannabinoid drugs under pharmaceutical development,
rising from 2 in 1995 to 27 in 2004 (Pacher et al., 2006).
The identification of a natural cannabinoid receptor–neuromodulator system in the body
was the key to pharmacological and therapeutic developments. Receptors are the sites
of action for brain chemicals, called neurotransmitters, and often the sites of action
of drugs. Binding of the neurotransmitter or drug to the brain cell receptor causes a
response in the cell. Two cannabis receptors (termed CB1 and CB2) have been found
(Pertwee, 1997). CB1 receptors are distributed in discrete areas of the brain, particularly
concentrated in the hippocampus and cerebral cortex (areas concerned with memory
and cognition), olfactory areas, basal ganglia and cerebellum (areas concerned with
motor activity and posture control) and the spinal cord. CB2 receptors are found
peripherally and are closely linked with cells in the immune system (Kumar et al., 2001).
With the discovery of cannabis receptors it became possible to develop cannabinoid
agonists or antagonists — that is, agents that activate or bind but do not activate the
receptors — that might act as therapeutic tools or help determine the roles of the
cannabinoid receptors and the body’s own endogenous cannabinoids (British Medical
Association, 1997). Two major endocannabinoids have been identified and isolated:
anandamide and 2-arachidonoyl glycerol. This endogenous cannabinoid system is
involved in analgesia, cognition, memory, locomotor activity, appetite, vomiting and
immune control (Kumar et al., 2001).
As the structure–activity relationships of the cannabis receptors and endocannabinoid
system unfolded, the potential for cannabis-based medicines became clearer. But in a
review of these developments, a leading neuropharmacologist, Professor Leslie Iversen,
suggested that pharmaceutical companies faced a range of substantial obstacles in
developing cannabis-based medications. These obstacles were: development costs would
be high; only synthetic cannabinoids could be patented rather than the natural product;
products would be likely to be niche drugs rather than ‘blockbuster’ drugs used to treat
common health problems; there were already medicines available to treat the problems
that cannabinoids might be used for; and finally, the vast US marketplace would be
difficult to enter, with the US having strict regulatory requirements to introduce a drug
that is derived from or chemically related to a prohibited substance (Iversen, 2003).
Over the last 30 years, widely reported use of illicitly smoked cannabis for selfmedication
for a range of illnesses has brought normally law-abiding citizens into
conflict with their country’s legal system. Surveys have found that the common
indications for cannabis use include depression, multiple sclerosis, pain, migraine,
asthma and cancer-related anorexia/cachexia (Schnelle et al., 1999; Gorter et al.,
2005).
The ethical dilemmas surrounding this issue were among the factors that led to
a number of enquiries examining the therapeutic potential of cannabis products. The
British Medical Association’s 1997 report Therapeutic Uses of Cannabis and the 1998
report Cannabis: the Scientific and Medical Evidence from a Select Committee of the
House of Lords both called for the setting up of clinical trials to evaluate the potential
therapeutic use of cannabinoids. The prestigious US Institute of Medicine published
its report Medical Use of Marijuana in 1999. Together, these reports established the
evidence base to support the further examination of cannabis products for medical use.
Medical and political interest intensified in several European countries and the medical
use of cannabis was legalised in the Netherlands in 2003 (Grotenhermen and Russo,
2002; Gorter et al., 2005) and extended for a five-year period in 2007.
Naturally, cannabis products are subject to the same rigorous clinical testing and
regulatory processes as any other potential medicine. Clinical trials for new medications
normally follow three phases. In phase I the safety of the drug is established. In phase II
the efficacy of the drug is established through giving the medication to a small group of
potential patients who have the condition targeted by the medication. Finally, phase III
trials use large studies involving hundreds of patients.
(for the rest of this article....)
http://www.emcdda.europa.eu/attachements.cfm/att_53382_EN_emcdda-cannabis-mon-vol1-ch2-web.pdf
Referenced as:
This publication should be referenced as:
EMCDDA (2008), A cannabis reader: global issues and local experiences, Monograph
series 8, Volume 1, European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
References to chapters in this monograph should include, where relevant, references to the
authors of each chapter, together with a reference to the wider publication. For example:
Corrigan, D. (2008), ‘The pharmacology of cannabis: issues for understanding its use’, in:
A cannabis reader: global issues and local experiences, Monograph series 8, Volume 1,
European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
The publication is available on the Internet at:
http://www.emcdda.europa.eu/publications/monographs/cannabis
Cataloguing data can be found at the end of this publication.
Luxembourg: Office for Official Publications of the European Communities, 2008
ISBN 978-92-9168-311-6
© European Monitoring Centre for Drugs and Drug Addiction, 2008
Reproduction is authorised provided the source is acknowledged.
Printed in Belgium
Rua da Cruz de Santa Apolónia 23–25, P-1149-045 Lisbon