Structure-Activity Relationship of Cannabis Derived Compounds for the Treatment of Neuronal Activity-Related Diseases

Prandi, Cristina; Blangetti, Marco; Namdar, Dvora; Koltai, Hinanit

doi:10.3390/molecules23071526

Cited by 36 publications

(59 citation statements)

References 102 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the beneficial combination of cannabidiol with Δ 9 -THC led to development of Sativex, a drug currently in clinical trials to treat a variety of indications including spasticity associated with multiple sclerosis ( Keating, 2017 ). In addition to Δ 9 -THC and cannabidiol, the cannabis plant contains hundreds of other phytocannabinoids and constituents not present in K2/Spice products that may help mitigate harmful and/or adverse effects ( Prandi et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

et al. 2018

View full text Add to dashboard Cite

Recreational use of marijuana is associated with few adverse effects, but abuse of synthetic cannabinoids (SCBs) can result in anxiety, psychosis, chest pain, seizures and death. To potentially explain higher toxicity associated with SCB use, we hypothesized that AB-PINACA, a common second generation SCB, exhibits atypical pharmacodynamic properties at CB1 cannabinoid receptors (CB1Rs) and/or a distinct metabolic profile when compared to Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive cannabinoid present in marijuana. Liquid chromatography tandem mass spectrometry (LC/MS) identified AB-PINACA and monohydroxy metabolite(s) as primary phase I metabolites (4OH-AB-PINACA and/or 5OH-AB-PINACA) in human urine and serum obtained from forensic samples. In vitro experiments demonstrated that when compared to Δ9-THC, AB-PINACA exhibits similar affinity for CB1Rs, but greater efficacy for G-protein activation and higher potency for adenylyl cyclase inhibition. Chronic treatment with AB-PINACA also results in greater desensitization of CB1Rs (e.g., tolerance) than Δ9-THC. Importantly, monohydroxy metabolites of AB-PINACA retain affinity and full agonist activity at CB1Rs. Incubation of 4OH-AB-PINACA and 5OH-AB-PINACA with human liver microsomes (HLMs) results in limited glucuronide formation when compared to that of JWH-018-M2, a major monohydroxylated metabolite of the first generation SCB JWH-018. Finally, AB-PINACA and 4OH-AB-PINACA are active in vivo, producing CB1R-mediated hypothermia in mice. Taken collectively, the atypical pharmacodynamic properties of AB-PINACA at CB1Rs relative to Δ9-THC (e.g., higher potency/efficacy and greater production of desensitization), coupled with an unusual metabolic profile (e.g., production of metabolically stable active phase I metabolites) may contribute to the pronounced adverse effects observed with abuse of this SCB compared to marijuana.

show abstract

Section: Discussionmentioning

confidence: 99%

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Δ9-Tetrahydrocannabinol (THC) and anandamide have the highest affinity for the CB1 receptor, while CBD exhibits low affinity for these receptors [20,21]. However, CBD has been proved to enhance endocannabinoid levels and indirectly activate CB receptors [8].…”

Section: Cannabinoids: Pharmacology and Generalitiesmentioning

confidence: 99%

“…Anandamide and 2-AG are reuptake via an extraneuronal monoamine membrane transporter (EMT); then, they are degraded by the fatty acid amide hydrolase (FAAH) and the monoacylglycerol lipase (MAGL), respectively [ 16 , 19 ]. Most known plant-derived cannabinoids include tetrahydrocannabinol (THC) and cannabidiol (CBD) [ 20 ]. These are tricyclic terpenoid compounds bearing a benzopyran moiety soluble in lipids and nonpolar organic solvents [ 20 , 21 ].…”

Section: Cannabinoids: Pharmacology and Generalitiesmentioning

confidence: 99%

See 1 more Smart Citation

Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review

Orrego-González

Londoño-Tobón

Ardila-González

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current chemotherapeutic options continue to have important side effects and may not be effective in preventing disease progression. Cannabinoids might be substances with possible therapeutic potential for cancer because they can attenuate the side effects of chemotherapy and have antiproliferative and antimetastatic effects. We aim to determine, through a systematic review of experimental studies performed on animal CRC models, if cannabinoids can reduce the formation of preneoplastic lesions (aberrant crypt foci), number, and volume of neoplastic lesions. Materials and Methods. A systematic, qualitative review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Scopus databases were searched. We use the following Medical Subject Headings (MESH) terms in PubMed: “colorectal neoplasms,” “colonic neoplasms,” “colorectal cancer,” “polyps,” “rimonabant,” “cannabidiol,” “cannabinoids,” “azoxymethane,” “xenograft,” and “mice.” Only studies that met the eligibility criteria were included. Results. Eight in vivo experimental studies were included in the analysis after the full-text evaluation. Seven studies were azoxymethane (AOM) colorectal cancer models, and four studies were xenograft models. Cannabidiol botanical substance (CBD BS) and rimonabant achieved high aberrant crypt foci (ACF) reduction (86% and 75.4%, respectively). Cannabigerol, O-1602, and URB-602 demonstrated a high capacity for tumor volume reduction. Induction of apoptosis, interaction with cell survival, growth pathways, and angiogenesis inhibition were the mechanisms extracted from the studies that explain cannabinoids’ actions on CRC. Conclusions. Cannabinoids have incredible potential as antineoplastic agents as experimental models demonstrate that they can reduce tumor volume and ACF formation. It is crucial to conduct more experimental studies to understand the pharmacology of cannabinoids in CRC better.

show abstract

“…Moreover, CB2 receptors are involved in neuroinflammation by modulating microglia activation and migration [74] and are consequently associated with neurodegenerative disorders [75]. Accordingly, CB2 receptor is seen as a potential therapeutic target for PD since it modulates the inflammatory process and does not trigger undesirable psychoactive effects [76,77]. Furthermore, several shreds of evidence suggest that cannabinoid compounds may interact with other receptors, besides CB1 and CB2, namely the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptors (PPARs) and the G-protein-coupled receptor (GPCR) [78,79].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease

Ferreira

Almeida²,

Tenreiro

et al. 2020

Life

View full text Add to dashboard Cite

Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology. Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide. However, the described clinical applications and safety of pharmacotherapy with cannabis products are yet to be fully supported by scientific evidence. Furthermore, the novel psychoactive substances are currently a popular alternative to classical drugs of abuse, representing an unknown health hazard for young adults who may develop PD later in their lifetime. This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs’ legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms.

show abstract

Structure-Activity Relationship of Cannabis Derived Compounds for the Treatment of Neuronal Activity-Related Diseases

Cited by 36 publications

References 102 publications

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review

Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease

Contact Info

Product

Resources

About