Abstract
The acid metabolites of THC were discovered almost 30 years ago and were later shown to posses modest analgesic and anti-inflammatory activity in a variety of models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a dimethylheptyl side chain is substituted for the pentyl side chain of the naturally occurring metabolite. It produces analgesia in the mouse hot plate, the PPQ writhing, the formalin and the tail clip assays. In the latter, it was equipotent to morphine; however, it showed a much greater duration of action. In the paw edema, subcutaneous air pouch and rat adjuvant-induced arthritis models of inflammation; it showed significant therapeutic activity at a dose of 0.2 mg/kg p.o. In the arthritis model it greatly reduced permanent damage to joints when compared to an indomethacin control as evidenced by an improved joint score over vehicle controls and by histopathological examination. In contrast to the NSAIDs, it was totally nonulcerogenic at therapeutically relevant doses. Moreover, it does not depress respiration, exhibit dependence, induce body weight loss or cause mutagenesis. It shows none of the typical actions in models of the psychotropic actions of cannabinoids suggesting that a good separation of desirable from undesirable effects was achieved. Studies on its mechanism of action are currently underway. The data thus far suggest the existence of a novel receptor for ajulemic acid with possible downstream effects on eicosanoid production, cytokine synthesis and metalloprotease activity. There is also circumstantial evidence for a putative endogenous ajulemic acid, namely, arachidonylglycine.
Keywords: Ajulemic Acid (CT3), Potent Analog, Acid Metabolites of THC, THC-11-oic acid, PPQ writhing, formalin, tail clip assays, NSAIDs, THC, ANALGESIC, ANTI INFLAMMATORY EFFECTS, (TNF)alpha and interleukin(IL)-1beta, TOXICITY, RECEPTOR, Chronic Ulcerogenic Effects, Indomethacin, Corpus, Antrum, Duodenum, Jejunum, Ileum, Colon, PUTATIVE ENDOGENOUS LIGANDS, Anandamide, N-arachidonyl glycine, Arachidonylglycine amide, Cyclooxygenase, Dimethylheptyl, Interleukin, Immunoreactive prostaglandin E, Non steroidal antiinflammatory drug, Para-phenylquinone, Platelet activating factor, Prostaglandin, Tetrahydrocannabinol, tumor necrosis factor
Current Pharmaceutical Design
Title: Ajulemic Acid (CT3) A Potent Analog of the Acid Metabolites of THC
Volume: 6 Issue: 13
Author(s): Sumner H. Burstein
Affiliation:
Keywords: Ajulemic Acid (CT3), Potent Analog, Acid Metabolites of THC, THC-11-oic acid, PPQ writhing, formalin, tail clip assays, NSAIDs, THC, ANALGESIC, ANTI INFLAMMATORY EFFECTS, (TNF)alpha and interleukin(IL)-1beta, TOXICITY, RECEPTOR, Chronic Ulcerogenic Effects, Indomethacin, Corpus, Antrum, Duodenum, Jejunum, Ileum, Colon, PUTATIVE ENDOGENOUS LIGANDS, Anandamide, N-arachidonyl glycine, Arachidonylglycine amide, Cyclooxygenase, Dimethylheptyl, Interleukin, Immunoreactive prostaglandin E, Non steroidal antiinflammatory drug, Para-phenylquinone, Platelet activating factor, Prostaglandin, Tetrahydrocannabinol, tumor necrosis factor
Abstract: The acid metabolites of THC were discovered almost 30 years ago and were later shown to posses modest analgesic and anti-inflammatory activity in a variety of models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a dimethylheptyl side chain is substituted for the pentyl side chain of the naturally occurring metabolite. It produces analgesia in the mouse hot plate, the PPQ writhing, the formalin and the tail clip assays. In the latter, it was equipotent to morphine; however, it showed a much greater duration of action. In the paw edema, subcutaneous air pouch and rat adjuvant-induced arthritis models of inflammation; it showed significant therapeutic activity at a dose of 0.2 mg/kg p.o. In the arthritis model it greatly reduced permanent damage to joints when compared to an indomethacin control as evidenced by an improved joint score over vehicle controls and by histopathological examination. In contrast to the NSAIDs, it was totally nonulcerogenic at therapeutically relevant doses. Moreover, it does not depress respiration, exhibit dependence, induce body weight loss or cause mutagenesis. It shows none of the typical actions in models of the psychotropic actions of cannabinoids suggesting that a good separation of desirable from undesirable effects was achieved. Studies on its mechanism of action are currently underway. The data thus far suggest the existence of a novel receptor for ajulemic acid with possible downstream effects on eicosanoid production, cytokine synthesis and metalloprotease activity. There is also circumstantial evidence for a putative endogenous ajulemic acid, namely, arachidonylglycine.
Export Options
About this article
Cite this article as:
Burstein H. Sumner, Ajulemic Acid (CT3) A Potent Analog of the Acid Metabolites of THC, Current Pharmaceutical Design 2000; 6 (13) . https://dx.doi.org/10.2174/1381612003399473
DOI https://dx.doi.org/10.2174/1381612003399473 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Loneliness and Social Isolation: Determinants of Cardiovascular Outcomes
Current Cardiology Reviews Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets Efficacy of Dexamethasone for the Treatment of COVID-19 Infection: A Perspective Review
Current Drug Delivery Modifiable Risk Factors for Premature Atherosclerosis in Systemic Lupus Erythematosus
Vascular Disease Prevention (Discontinued) Prostaglandin E2 Receptors as Potential Bone Anabolic Targets – Selective EP4 Receptor Agonists
Current Molecular Pharmacology Systemic Inflammatory Response as a Risk and Prognosis Factor in Ventilator-Associated Pneumonia
Current Respiratory Medicine Reviews Role of Nitric Oxide and Reactive Oxygen Species in Arthritis
Current Pharmaceutical Design Antiviral Treatment of HCV Carriers with Persistently Normal ALT Levels
Mini-Reviews in Medicinal Chemistry Pharmacogenomics and the Treatment of Sporadic Alzheimers Disease:A Decade of Progress
Current Pharmacogenomics and Personalized Medicine Azathioprine in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Emerging Strategies and Challenges for Controlled Delivery of Taxanes: A Comprehensive Review
Current Drug Metabolism Pertinence of Apoptosis Markers for the Improvement of In Vitro Fertilization (IVF)
Current Medicinal Chemistry Possible Pathways of Hepatotoxicity Caused by Chemical Agents
Current Drug Metabolism G-Protein Signaling, Lipid Rafts and the Possible Sites of Action for the Antidepressant Effects of n-3 Polyunsaturated Fatty Acids
CNS & Neurological Disorders - Drug Targets Contribution of Inflammatory Processes to Nerve Cell Toxicity by Bilirubin and Efficacy of Potential Therapeutic Agents
Current Pharmaceutical Design Recent Advances in Targeting Viral Proteases for the Discovery of Novel Antivirals
Current Topics in Medicinal Chemistry Induced Stem Cells as a Novel Multiple Sclerosis Therapy
Current Stem Cell Research & Therapy Nitric Oxide Production and Signaling in Inflammation
Current Drug Targets - Inflammation & Allergy ADME Optimization and Toxicity Assessment in Early- and Late-Phase Drug Discovery
Current Topics in Medicinal Chemistry The Use of the Zebrafish Model to Aid in Drug Discovery and Target Validation
Current Topics in Medicinal Chemistry