Professor Roger Pertwee | The University of Aberdeen

Professor Roger Pertwee

Emeritus Professor

Email Address: rgp@abdn.ac.uk
Office Address: School of Medical Sciences Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB25 2ZD Scotland, UK
School/Department: School of Medicine, Medical Sciences and Nutrition

Biography

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 now an Emeritus Professor at the University of Aberdeen, where he is still actively engaged in scientific research. He is also co-chairman of the International Union of Basic and Clinical Pharmacology (IUPHAR) Subcommittee on Cannabinoid Receptors, a co-ordinator of the British Pharmacological Society’s Special Interest Group on Cannabinoids, a co-founder of the International Cannabinoid Research Society (ICRS) <http://icrs.co/> , and an invited scientific advisor on cannabinoid pharmacology/therapeutics to the Beckley Foundation <http://beckleyfoundation.org/about/advisory-boards/>, has had formal cannabinoid pharmacology-related links with several pharmaceutical companies, and currently has such a link with GW Pharmaceuticals. He has served too, twice as President of the ICRS (1997-1998 and 2007-2008), and once as Chairman of the International Association for Cannabinoid Medicines (IACM; 2005-2007), and is also currently ICRS International Secretary, and a member of the IACM Board of Directors <http://www.cannabis-med.org/index.php?tpl=page&id=74&lng=en>. He was the recipient of the 2002 Mechoulam Award “for his outstanding contributions to cannabinoid research”. He was also awarded the 2011 Wellcome Gold Medal by the British Pharmacological Society (BPS) “for outstanding contributions to pharmacology, based mainly on research achievements”, and the 2013 IACM Special Award “for his major contributions to the re-introduction of cannabis as a medicine”, and is an Honorary Fellow of the BPS: this fellowship is awarded to BPS members who have “demonstrated distinction and peer recognition in science, or have given long and valuable service to the Society”. In addition, he was identified by Thomson Reuters in 2005 to be a “Highly Cited Researcher” and hence among “the world's most cited and influential researchers”. He also received (1) a Highly Cited Researcher Award from Thomson Reuters in September 2014 “in recognition of ranking among the top 1% of researchers for most cited documents in their specific field” (see Pertwee in “Archives” at <http://hcr.stateofinnovation.thomsonreuters.com/page/archives> and from Clarivate Analytics in 2018 “in recognition of exceptional research performance demonstrated by production of multiple highly cited papers, those that rank in the top 1% by citations for field and year in Pharmacology and Toxicology” and (2) the 2018 Lifetime Achievement Award from the International Cannabinoid Research Society "for outstanding contributions to cannabinoid research and the ICRS".

Roger Pertwee presented evidence on cannabis in person at the House of Lords to the Science and Technology Committee which published its report on cannabis in 1998. He is the author of numerous review articles on the cannabinoids and is often invited to speak on the pharmacology of cannabinoids at international conferences. He is also interested in the therapeutic potential of cannabinoids. Indeed, he was a contributing author of the British Medical Association book entitled "Therapeutic Uses of Cannabis." and served on the Royal Pharmaceutical Society working party that recommended and helped to design clinical trials with cannabis and THC that were carried out in the UK and funded by the Medical Research Council. Together with Drs Rik Musty and Paul Consroe he also carried out the first large survey of multiple sclerosis patients who self-medicate with cannabis [Eur Neurol (1997) 38: 44]. His contributions to the "medicalization of cannabis" are summarized in a Witness Seminar Transcript (Vol 40), co-authored by Crowther, S.M., Reynolds, L.A. and Tansey, E.M. and published in 2010 by The Wellcome Trust Centre for the History of Medicine at UCL. This book is freely downloadable at <http://www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/volume40/index.html>.

Roger Pertwee's research focuses on the pharmacology of cannabinoids. He began his work in this area in 1968 as a post-doc with Professor Sir William Paton at the Department of Pharmacology, Oxford University. He initially worked with cannabis and also with delta-9-tetrahydrocannabinol (THC) and cannabidiol, both of which were extracted from tincture of cannabis, then still a legal medicine in the UK. This research led to the demonstration that cannabidiol is a highly effective inhibitor of hepatic microsomal enzymes and to the development of the "ring immobility test", still widely used as a behavioural bioassay.

After moving to Aberdeen in 1974, Roger Pertwee continued with his cannabinoid research, initially investigating the basis for the hypothermic effect of THC. This work provided evidence that THC lowers the thermoregulatory set point such that animals regulate their core temperature at a lower level than normal by adjusting heat gain and heat loss both autonomically and behaviourally. In other research carried out during this time he found that cannabinoids interact synergistically with benzodiazepines and also identified the globus pallidus as one of the sites at which cannabinoids alter motor function.

Opioid research with the mouse isolated vas deferens being carried out in Professor Hans Kosterlitz's laboratory in Aberdeen gave Roger Pertwee the opportunity to establish whether this tissue would also serve as a bioassay for cannabinoids. The mouse vas deferens turned out to be an extremely sensitive quantitative assay for CB₁ agonists. He presented some of the initial vas deferens data at a cannabinoid meeting in Palm Beach in 1991 and this led to a collaboration with Professor Raphael Mechoulam who was also at the meeting. As a result, using the mouse vas deferens, Roger Pertwee (with Graeme Griffin) was able to provide the first evidence that anandamide not only binds to cannabinoid receptors (Dr William Devane's data) but also activates these receptors, greatly strengthening the argument that anandamide is an endogenous cannabinoid/endocannabinoid [Science (1992) 258:1946]. Other research in his laboratory, led by Dr Angela Coutts, was directed at mapping out the distribution of cannabinoid receptors in brain and gut using immunohistochemical techniques.

His research has also played major roles in

the discovery that ethanolamides that are formed from dietary omega-3 polyunsaturated fatty acids and that seem to be endocannabinoids, have the capacity to inhibit cancer cell growth and proliferation;
the discovery of a cannabinoid CB₁ receptor allosteric site;
the discovery that delta-9-tetrahydrocannabivarin is a plant cannabinoid (phytocannabinoid) - and that this compound is both a cannabinoid CB₁ receptor blocker (antagonist) and a cannabinoid CB₂ receptor activator (agonist) that has the potential to treat drug dependence, Parkinson’s disease, stroke, obesity and liver diseases, and to reduce health risks associated with liver transplantation;
the pharmacological characterization of other phytocannabinoids, including cannabidiol, cannabidiolic acid & cannabigerol, and the further pharmacological characterization of THCV;
the discovery/pharmacological characterization of novel synthetic cannabinoids many of which are widely used by cannabinoid researchers as experimental tools, e.g.

methanandamide, the first CB₁ receptor-selective agonist (with Dr Alexandros Makriyannis);
two other CB₁-selective agonists: ACEA & ACPA (with Dr Cecelia Hillard);
HU-308, a CB₂-selective agonist (with Dr Raphael Mechoulam);
AM281, a widely-used CB₁ receptor antagonist, and AM630, a widely-used CB₂ receptor antagonist (with Dr Alexandros Makriyannis);
CB₁ receptor “neutral” antagonists;
O-1057, the first water-soluble cannabinoid receptor ligand (with Drs Billy Martin and Raj Razdan);
novel positive and negative allosteric modulators of the CB₁ receptor (with Dr Ganesh Thakur).

Research now being carried out in Roger Pertwee's laboratory is directed (i) at seeking out further pharmacological actions of phytocannabinoids, (ii) at elucidating the pharmacological actions of other constituents of cannabis, and (iii) at exploring the actions and therapeutic potential of novel synthetic allosteric modulators of cannabinoid receptors. This research, which is being conducted mainly using radioligand binding assays and in vitro bioassays that measure drug effects on cannabinoid receptor signalling (e.g. [³⁵S]GTPgammaS binding assays), is currently supported by the US National Institute on Drug Abuse (part of NIH) and by GW Pharmaceuticals. He is also presently collaborating with colleagues at Aberdeen University in cannabinoid research funded by Diabetes UK and by Medical Research Scotland.

Research

Research Overview

Primary research interests:

· pharmacology and therapeutic potential of plant cannabinoids

· pharmacology of allosteric sites on cannabinoid receptors

· novel cannabinoid CB₁ and CB₂ receptor ligands

· new pharmacological targets for cannabinoids

· roles of the endocannabinoid system in health and disease

Current Research

Roger Pertwee's current research is directed at seeking out pharmacological actions of phytocannabinoids, and at elucidating the pharmacological actions of other constituents of cannabis. In addition, he is currently following up a discovery made in his laboratory that there is at least one allosteric site on the cannabinoid CB1 receptor, by exploring the actions and therapeutic potential of novel synthetic allosteric modulators of cannabinoid receptors.

Publications

Update

Biography

Research Overview

Current Research

Cyclic AMP Assay Using Human Cannabinoid CB2 Receptor-Transfected Cells

Displacement Binding Assay Using Human Cannabinoid CB2 Receptor-Transfected Cells

The Plant Derived 3-3′-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models

M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter

Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex

Osteogenic growth peptide is a potent anti-inflammatory and bone preserving hormone via cannabinoid receptor type 2

Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity

Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion

Disease associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue specific activity of the cannabinoid‐1 receptor gene promoter; implications for cannabinoid pharmacogenetics

Fatty acid suppression of glial activation prevents central neuropathic pain after spinal cord injury

Disruption of an enhancer associated with addictive behaviour within the cannabinoid receptor-1 gene suggests a possible role in alcohol intake, cannabinoid response and anxiety-related behaviour

A synthetic analogue of cannabidiolic acid that acts like a positive allosteric modulator at 5-HT1A receptors

Identification of the First Synthetic Allosteric Modulator of the CB2 Receptors and Evidence of Its Efficacy for Neuropathic Pain Relief

Positive Allosteric Modulation of Cannabinoid Receptor Type 1 Suppresses Pathological Pain Without Producing Tolerance or Dependence

Enantiospecific Allosteric Modulation of Cannabinoid 1 Receptor

Synthesis, radio-synthesis and in vitro evaluation of terminally fluorinated derivatives of HU-210 and HU-211 as novel candidate PET tracers

The pharmacology and therapeutic potential of plant cannabinoids

Exploring the Benzimidazole Ring as a Substitution for Indole in Cannabinoid Allosteric Modulators

Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages

Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant and Signaling Profile of GAT100, a Novel, Potent, and Irreversibly Binding Probe

The Displacement Binding Assay Using Human Cannabinoid CB2 Receptor-Transfected Cells

Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence

Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s)

The Cyclic AMP Assay Using Human Cannabinoid CB2 Receptor-Transfected Cells

Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency

Modulation of food consumption and sleep-wake cycle in mice by the neutral CB1 antagonist ABD459

The phytocannabinoid, Δ(9) -tetrahydrocannabivarin, can act through 5-HT1 A receptors to produce antipsychotic effects

Tricyclic fused pyrazoles with a 'Click' 1,2,3-triazole substituent in position 3 are nanomolar CB1 receptor ligands

Are cannabidiol and Delta(9)-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review

Endocannabinoids

Early phytocannabinoid chemistry to endocannabinoids and beyond

Pyrazoles with a "click" 4-[N-(4-fluorobutyl)-1,2,3-triazole] substituent in position 3 are nanomolar CB1 receptor ligands

Structure-affinity relationships and pharmacological characterization of new alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual cannabinoid receptor/TRPA1 channel agonist

The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act trough 5HT1A receptors to produce anti-psychotic effects

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol

In-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569

Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications

Handbook of Cannabis

Motor effects of the non-psychotropic phytocannabinoid cannabidiol that are mediated by 5-HT1A receptors

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism

Effects of Δ9-tetrahydrocannabivarin at serotoninergic 5-HT1A receptors, and of its 11-Hydroxy-metabolite at cannabinoid CB1 and CB2 receptors

Characterization of cannabinoid receptor ligands in tissues natively expressing cannabinoid CB2 receptors

The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation

CB1 Receptor Allosteric Modulators Display Both Agonist and Signaling Pathway Specificity

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities

Investigations on the 4-quinolone-3-carboxylic acid motif. 6. Synthesis and pharmacological evaluation of 7-substituted quinolone-3-carboxamide derivatives as high affinity ligands for cannabinoid receptors

Manipulation of the endocannabinoid system to provide a protective benefit in the MPTP-mouse model

Investigations on the 4-Quinolone-3-Carboxylic Acid Motif Part 5: Modulation of the Physicochemical Profile of a Set of Potent and Selective Cannabinoid-2 Receptor Ligands through a Bioisosteric Approach

AM630 behaves as a protean ligand at the human cannabinoid CB2 receptor

Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus

Delta(8)-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors

Sativex-like Combination of Phytocannabinoids is Neuroprotective in Malonate-Lesioned Rats, an Inflammatory Model of Huntington's Disease: Role of CB1 and CB2 Receptors

Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids

The endocannabinoid 2-AG provides neuroprotection in the MPTP model of Parkinson's disease

Resorcinol-sn-glycerol derivatives: Novel 2-Arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor

Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines

N-(ARYLALKYL)-1H-INDOLE-2-SULFONIC ACID AMIDE COMPOUNDS AND THEIR THERAPEUTIC USE AS CANNABINOID ALLOSTERIC MODULATORS

Structural and pharmacological analysis of O-2050, a putative neutral cannabinoid CB(1) receptor antagonist

The function of the endocannabinoid system

The endocannabinoid 2-AG provides neuroprotection in the MPTP model of Parkinson's disease

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2

Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines

Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands.

Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase

Phytocannabinoids beyond the Cannabis plant - do they exist?

The effects of ¿9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

WIN55,212-2 induced deficits in spatial learning are mediated by cholinergic hypofunction

In vitro and in vivo pharmacological characterization of two novel selective cannabinoid CB2 receptor inverse agonists

Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist

Receptors and Channels Targeted by Synthetic Cannabinoid Receptor Agonists and Antagonists

Conformationally Constrained Fatty Acid Ethanolamides as Cannabinoid and Vanilloid Receptor Probes

Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice

Cyclic AMP Assay Using Human Cannabinoid CB₂ Receptor-Transfected Cells

Displacement Binding Assay Using Human Cannabinoid CB₂ Receptor-Transfected Cells

Identification of the First Synthetic Allosteric Modulator of the CB₂ Receptors and Evidence of Its Efficacy for Neuropathic Pain Relief

Pure Δ⁹-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ⁹-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages

The Cyclic AMP Assay Using Human Cannabinoid CB₂ Receptor-Transfected Cells

AM630 behaves as a protean ligand at the human cannabinoid CB₂ receptor

Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT_1A somatodendritic autoreceptors in the dorsal raphe nucleus

The plant cannabinoid Δ⁹-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

Evidence that the plant cannabinoid cannabigerol is a highly potent α₂-adrenoceptor agonist and moderately potent 5HT_1A receptor antagonist

Cannabidiol targets mitochondria to regulate intracellular Ca²⁺ levels

Cannabidiol displays unexpectedly high potency as an antagonist of CB₁ and CB₂ receptor agonists in vitro