A long-standing goal in cannabinoid research has been the discovery of potent synthetic analogs of the natural substances that might be developed as clinically useful drugs. This requires, among other things, that they be free of the psychotropic effects that characterize the recreational use of Cannabis. An important driving force for this goal is the long history of the use of Cannabis as a medicinal agent especially in the treatment of pain and inflammation. While few compounds appear to have these properties, ajulemic acid (AJA), also known as CT-3 and IP-751, is a potential candidate that could achieve this goal. Its chemical structure was derived from that of the major metabolite of Delta9-THC, the principal psychotropic constituent of Cannabis. In preclinical studies it displayed many of the properties of non-steroidal anti-inflammatory drugs (NSAIDs); however, it seems to be free of undesirable side effects. The initial short-term trials in healthy human subjects, as well as in patients with chronic neuropathic pain, demonstrated a complete absence of psychotropic actions. Moreover, it proved to be more effective than placebo in reducing this type of pain as measured by the visual analog scale. Unlike the narcotic analgesics, signs of dependency were not observed after withdrawal of the drug at the end of the one-week treatment period. Data on its mechanism of action are not yet complete; however, the activation of PPAR-gamma, and regulation of eicosanoid and cytokine production, appear to be important for its potential therapeutic effects.
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Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study.
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Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
Article Synopsis
- - Dermatomyositis (DM) is a rare autoimmune disease affecting the skin and is often difficult to treat, with standard medications sometimes ineffective; lenabasum, a selective cannabinoid receptor 2 agonist, shows promise in managing these skin-related symptoms.
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Evaluating the Abuse Potential of Lenabasum, a Selective Cannabinoid Receptor 2 Agonist.
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Department of Psychiatry, Columbia University Irving Medical Center, New York, New York (R.L., S.D.C.); Division on Substance Use Disorders, New York State Psychiatric Institute and Columbia University, New York, New York (R.L., G.M., R.S., S.D.C.); and Corbus Pharmaceuticals, Norwood, Massachusetts (A.K., I.H.).
Endocannabinoids, which are present throughout the central nervous system (CNS), can activate cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases. However, careful evaluation of abuse potential is necessary.
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College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, P.R. China.
Background: Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases.
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Cannabinoid metabolites have been reported to be more potent than their parent compounds. Among them, ajulemic acid (AJA) is a side-chain analog of Δ-THC-11-oic acid, which would be a good template structure for the discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield.
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In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity.
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