Medical Cannabis and Cannabinoids最新文献

{"title":"Perspectives on Challenges in Cannabis Drug Delivery Systems: Where Are We?","authors":"Manikandan Palrasu,&nbsp;Lillianne Wright,&nbsp;Manish Patel,&nbsp;Lindsey Leech,&nbsp;Scotty Branch,&nbsp;Shea Harrelson,&nbsp;Saeed Khan","doi":"10.1159/000525629","DOIUrl":"https://doi.org/10.1159/000525629","url":null,"abstract":"<p><p>Cannabis and its natural derivatives have emerged as promising therapeutics for multiple pathological and nonpathological medical conditions. For example, cannabinoids, the most popular and biologically active chemicals in cannabis, aid in many clinical ailments, including pain, inflammation, epilepsy, sleep disturbances or insomnia, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, anti-nausea, and most importantly, cancer. Despite the comprehensive benefits, certain aspects of cannabis present unique challenges in the medical cannabis landscape. Recent studies have highlighted the inherent challenges associated with cannabinoids' formulation like low solubility, rapid metabolism, poor bioavailability, and erratic pharmacokinetics - all of which contribute to the limited efficacy of cannabinoids. Several efforts are underway to address the bottlenecks and modify the formulations along with the delivery systems to achieve greater solubility/bioavailability, potency, and efficacy in treatment settings while minding the necessary standards for purity associated with the pharmaceutical industry. The current article presents a perspective on (1) a working knowledge of cannabinoids and their mechanisms of action, (2) the landscape of using medicinal cannabis for cancer-related medical conditions along with adversities, (3) current approaches, formulations, and challenges in medicinal cannabis delivery systems (oral, transdermal, pulmonary, and transmucosal), and lastly, (4) emerging approaches to improve delivery systems.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"102-119"},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/84/mca-0005-0102.PMC9710325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35209429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Quality of Life in Adults Initiating Medical Marijuana Treatment.","authors":"Lydia S Buonomano,&nbsp;Matthew M Mitnick,&nbsp;Thomas R McCalmont,&nbsp;Paulina Syracuse,&nbsp;Karen L Dugosh,&nbsp;David S Festinger,&nbsp;Michelle R Lent","doi":"10.1159/000524831","DOIUrl":"https://doi.org/10.1159/000524831","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the rising availability and use of medical marijuana (MM) in the USA, little is known about the demographics, clinical characteristics, or quality of life of MM patients. This study describes the demographic characteristics and health-related quality of life (HRQoL) of MM patients who are initiating treatment in Pennsylvania.</p><p><strong>Methods: </strong>Two-hundred adults naive to MM and referred for any of the 23 state-approved qualifying conditions were recruited at three MM dispensaries in Pennsylvania between September 2020 and March 2021. All participants consented to the study; completed semi-structured interviews that included demographic questionnaires, the Short Form-36 (SF-36), and Generalized Anxiety Disorder-7 (GAD-7); provided height and weight measurements; and allowed access their dispensary medical records.</p><p><strong>Results: </strong>Participants had a mean age of 48.5 ± 15.6 years, predominantly identified as female (67.5%), and were most commonly referred for chronic pain (63.5%) and/or anxiety (58.5%). Additionally, 46.0% were living with obesity as determined by BMI. Relative to a normative sample, participants reported diminished HRQoL in several domains, most notably in role limitations due to physical health (<i>M</i> = 46.0 ± 42.0), role limitations due to emotional problems (<i>M</i> = 52.5 ± 42.3), energy and fatigue (<i>M</i> = 39.8 ± 20.2), and pain (<i>M</i> = 49.4 ± 26.0).</p><p><strong>Discussion/conclusion: </strong>Patients initiating MM treatment experienced low HRQoL in multiple domains. Future studies could evaluate the relationship between HRQoL and patients' decisions to pursue MM treatment, as well as changes in HRQoL with MM use over time.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247440/pdf/mca-0005-0095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40617079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities","authors":"Tess Puopolo, Chang Liu, Hang Ma, N. Seeram","doi":"10.1159/000524086","DOIUrl":"https://doi.org/10.1159/000524086","url":null,"abstract":"Introduction: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate and choline at the neuromuscular junction. Abnormal hyperactivity of AChE and BChE can lead to cholinergic deficiency, which is associated with several neurological disorders including cognitive decline and memory impairments. Preclinical studies support that some cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC) may exert pharmacological effects on the cholinergic system, but it remains unclear whether cannabinoids can inhibit AChE and BChE activities. Herein, we aimed to evaluate the inhibitory effects of a panel of cannabinoids including CBD, Δ8-THC, cannabigerol (CBG), cannabigerolic acid (CBGA), cannabicitran (CBT), cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) on AChE and BChE activities. Methods: The inhibitory effects of cannabinoids on the activities of AChE and BChE enzymes were evaluated with the Ellman method using acetyl- and butyryl-thiocholines as substrates. The inhibition mechanism of cannabinoids on AChE and BChE was studied with enzyme kinetic assays including the Lineweaver-Burk and Michaelis-Menten analyses. In addition, computational-based molecular docking experiments were performed to explore the interactions between the cannabinoids and the enzyme proteins. Results: Cannabinoids including CBD, Δ8-THC, CBG, CBGA, CBT, CBDV, CBC, and CBN (at 200 µM) inhibited the activities of AChE and BChE by 70.8, 83.7, 92.9, 76.7, 66.0, 79.3, 13.7, and 30.5%, and by 86.8, 80.8, 93.2, 87.1, 77.0, 78.5, 27.9, and 22.0%, respectively. The inhibitory effects of these cannabinoids (with IC50 values ranging from 85.2 to >200 µM for AChE and 107.1 to >200 µM for BChE) were less potent as compared to the positive control galantamine (IC50 1.21 and 6.86 µM for AChE and BChE, respectively). In addition, CBD, as a representative cannabinoid, displayed a competitive type of inhibition on both AChE and BChE. Data from the molecular docking studies suggested that cannabinoids interacted with several amino acid residues on the enzyme proteins, which supported their overall inhibitory effects on AChE and BChE. Conclusion: Cannabinoids showed moderate inhibitory effects on the activities of AChE and BChE enzymes, which may contribute to their modulatory effects on the cholinergic system. Further studies using cell-based and in vivo models are warranted to evaluate whether cannabinoids’ neuroprotective effects are associated with their anti-cholinesterase activities.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"85 - 94"},"PeriodicalIF":0.0,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42104819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Consuming Cannabis Flower for Treatment of Fatigue","authors":"Xiaoxue Li, Jegason P. Diviant, Sarah S. Stith, Franco Brockelman, Keenan Keeling, Branden Hall, J. Vigil","doi":"10.1159/000524057","DOIUrl":"https://doi.org/10.1159/000524057","url":null,"abstract":"Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals’ metabolic states and the synergistic chemotypic properties of the plant.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"76 - 84"},"PeriodicalIF":0.0,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42729199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?","authors":"W. Zieglgänsberger, R. Brenneisen, A. Berthele, C. Wotjak, B. Bandelow, T. Tölle, B. Lutz","doi":"10.1159/000522432","DOIUrl":"https://doi.org/10.1159/000522432","url":null,"abstract":"The development of a high-end cannabinoid-based therapy is the result of intense translational research, aiming to convert recent discoveries in the laboratory into better treatments for patients. Novel compounds and new regimes for drug treatment are emerging. Given that previously unreported signaling mechanisms for cannabinoids have been uncovered, clinical studies detailing their high therapeutic potential are mandatory. The advent of novel genomic, optogenetic, and viral tracing and imaging techniques will help to further detail therapeutically relevant functional and structural features. An evolutionarily highly conserved group of neuromodulatory lipids, their receptors, and anabolic and catabolic enzymes are involved in a remarkable variety of physiological and pathological processes and has been termed the endocannabinoid system (ECS). A large body of data has emerged in recent years, pointing to a crucial role of this system in the regulation of the behavioral domains of acquired fear, anxiety, and stress-coping. Besides neurons, also glia cells and components of the immune system can differentially fine-tune patterns of neuronal activity. Dysregulation of ECS signaling can lead to a lowering of stress resilience and increased incidence of psychiatric disorders. Chronic pain may be understood as a disease process evoked by fear-conditioned nociceptive input and appears as the dark side of neuronal plasticity. By taking a toll on every part of your life, this abnormal persistent memory of an aversive state can be more damaging than its initial experience. All strategies for the treatment of chronic pain conditions must consider stress-related comorbid conditions since cognitive factors such as beliefs, expectations, and prior experience (memory of pain) are key modulators of the perception of pain. The anxiolytic and anti-stress effects of medical cannabinoids can substantially modulate the efficacy and tolerability of therapeutic interventions and will help to pave the way to a successful multimodal therapy. Why some individuals are more susceptible to the effects of stress remains to be uncovered. The development of personalized prevention or treatment strategies for anxiety and depression related to chronic pain must also consider gender differences. An emotional basis of chronic pain opens a new horizon of opportunities for developing treatment strategies beyond the repeated sole use of acutely acting analgesics. A phase I trial to determine the pharmacokinetics, psychotropic effects, and safety profile of a novel nanoparticle-based cannabinoid spray for oromucosal delivery highlights a remarkable innovation in galenic technology and urges clinical studies further detailing the huge therapeutic potential of medical cannabis (Lorenzl et al.; this issue).","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"61 - 75"},"PeriodicalIF":0.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44122802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannx Conference abstracts","authors":"","doi":"10.1159/000522395","DOIUrl":"https://doi.org/10.1159/000522395","url":null,"abstract":"All abstracts are in the attached word document<br />Med Cannabis Cannabinoids 2022;5:36–60","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Will Cannabis or Cannabinoids Protect You from SARS-CoV-2 Infection or Treat COVID-19?","authors":"Joshua D. Brown, A. Goodin","doi":"10.1159/000522472","DOIUrl":"https://doi.org/10.1159/000522472","url":null,"abstract":"• A recent study reported that two cannabinoids, cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), could block cellular entry of the virus that causes COVID-19 during in vitro experiments using cell cultures in a laboratory • There is a low likelihood of translating these preclinical research findings to cannabinoid-based therapies due to clinical and pragmatic concerns with dosing that render CBDA and CBGA (as well as other cannabinoids) to be unlikely candidates for further drug development. These include, for example, a short half-life of CBDA, requiring frequent dosing intervals; high doses required at each interval to match the inhibitory concentrations studied; and high cost and lack of availability of CBDA and CBGA. • Replicating the observed effects in the complex human body is unlikely due to the interplay of these compounds within the endocannabinoid system, and there are known and hypothesized safety concerns for the doses required. • Cannabinoids, including CBDA and CBGA, are not recommended for the treatment or prevention of SARS-CoV-2 infection. • Recreational or medical use of currently available cannabis-derived products are at doses much lower than those studied and are unlikely to provide any benefit against SARS-CoV-2 infection. DOI: 10.1159/000522472","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"32 - 35"},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46945580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation.","authors":"Sarah Abelev,&nbsp;Leon N Warne,&nbsp;Melissa Benson,&nbsp;Mark Hardy,&nbsp;Sunny Nayee,&nbsp;John Barlow","doi":"10.1159/000521492","DOIUrl":"https://doi.org/10.1159/000521492","url":null,"abstract":"<p><strong>Introduction: </strong>Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS).</p><p><strong>Objectives: </strong>We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time.</p><p><strong>Results: </strong>More than half (<i>n</i> = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (<i>p</i> = 0.034), and pain intensity scores verged on significance (<i>p</i> = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%).</p><p><strong>Conclusion: </strong>This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"20-31"},"PeriodicalIF":0.0,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235063/pdf/mca-0005-0020.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40617080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery","authors":"S. Lorenzl, Franz Gottwald, Angelika Nistler, Laura Brehm, Renate Grötsch, Georg Haber, Christian Bremm, Christiane Weck, Carina Trummer, Werner Brand","doi":"10.1159/000521352","DOIUrl":"https://doi.org/10.1159/000521352","url":null,"abstract":"Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50–2.68) and AUC0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"9 - 19"},"PeriodicalIF":0.0,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoids as Cocrystals","authors":"C. N. Filer","doi":"10.1159/000521137","DOIUrl":"https://doi.org/10.1159/000521137","url":null,"abstract":"Dear Editor, The fascinating portfolio of Cannabis cannabinoids (phytocannabinoids) [1] continues to grow with new members continually added [2]. Interest in these intriguing natural products has accelerated in recent years, fueled by their potential as medicinal agents [3]. However, along with the promising pharmaceutical opportunity for cannabinoids come some challenging chemistry issues. The first concern is a common property shared by most cannabinoids, namely, their physical state as lipophilic, low melting point semisolids. This physical nature has profound implications. Since crystalline substances are usually more stable than amorphous solids, many cannabinoids have stability limitations. Acidic cannabinoids (functionalized with an aromatic carboxyl [CO2H] group) are especially prone to decarboxylation, but even neutral cannabinoids (lacking a carboxyl group) can be unstable to heat or light. With an estimated 70% of pharmaceuticals given as tablets [4], the low melting point-semisolid state of most cannabinoids has certainly complicated this convenient administration route for them. Another consequence of the cannabinoid lipophilic nature is their lack of water solubility. In fact, limited water solubility with accompanying delay of drug absorption and bioavailability has been a major problem for many candidate pharmaceuticals like the cannabinoids [5]. Finally, the large number (but smaller individual amounts) of “minor cannabinoids” as a complex mixture in the Cannabis trichomes has confounded their purification and hindered their pharmaceutical development. The purpose of this note is to highlight a recent and exciting alternative approach to these various technical challenges. Ongoing efforts by cannabinoid chemists to address these daunting obstacles have usually focused on each of them individually. However, the recent return to the 19th century chemistry of “cocrystallization” may well be able to solve some of them simultaneously. This transformative technique is significantly different from traditional crystallization. Cocrystallization involves the intermolecular noncovalent bonding of a molecule of interest (like a cannabinoid) with a companion neutral partner molecule (often termed a “coformer”), crystallizing as a stoichiometric pair in a well-defined and repeating 3-dimensional cocrystal lattice. The discovery of cocrystals is widely attributed to noted German chemist Friedrich Wohler [6] in 1844 and his preparation of quinhydrone, a cocrystal redox couple of quinone and hydroquinone. Wohler was likely unaware of his discovery’s significance and the full characterization of quinhydrone as a cocrystal (by X-ray crystal analysis) took more than a century to accomplish. Cocrystal technology with its many synthetic methods has now been eagerly embraced by the pharmaceutical sector to improve drug stability and bioavailability [7]. Interestingly, early indications that cannabinoids might","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"7 - 8"},"PeriodicalIF":0.0,"publicationDate":"2022-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48520845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}