The phytocannabinoids of
L. have, since ancient times, been proposed as a pharmacological alternative for treating various central nervous system (CNS) disorders. Interestingly, cannabinoid receptors ...(CBRs) are highly expressed in the basal ganglia (BG) circuit of both animals and humans. The BG are subcortical structures that regulate the initiation, execution, and orientation of movement. CBRs regulate dopaminergic transmission in the
pathway and, thus, the BG circuit also. The functioning of the BG is affected in pathologies related to movement disorders, especially those occurring in Parkinson's disease (PD), which produces motor and non-motor symptoms that involving GABAergic, glutamatergic, and dopaminergic neural networks. To date, the most effective medication for PD is levodopa (l-DOPA); however, long-term levodopa treatment causes a type of long-term dyskinesias, l-DOPA-induced dyskinesias (LIDs). With neuromodulation offering a novel treatment strategy for PD patients, research has focused on the endocannabinoid system (ECS), as it participates in the physiological neuromodulation of the BG in order to control movement. CBRs have been shown to inhibit neurotransmitter release, while endocannabinoids (eCBs) play a key role in the synaptic regulation of the BG. In the past decade, cannabidiol (CBD), a non-psychotropic phytocannabinoid, has been shown to have compensatory effects both on the ECS and as a neuromodulator and neuroprotector in models such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and reserpine, as well as other PD models. Although the CBD-induced neuroprotection observed in animal models of PD has been attributed to the activation of the CB1 receptor, recent research conducted at a molecular level has proposed that CBD is capable of activating other receptors, such as CB2 and the TRPV-1 receptor, both of which are expressed in the dopaminergic neurons of the
pathway. These findings open new lines of scientific inquiry into the effects of CBD at the level of neural communication. Cannabidiol activates the PPARγ, GPR55, GPR3, GPR6, GPR12, and GPR18 receptors, causing a variety of biochemical, molecular, and behavioral effects due to the broad range of receptors it activates in the CNS. Given the low number of pharmacological treatment alternatives for PD currently available, the search for molecules with the therapeutic potential to improve neuronal communication is crucial. Therefore, the investigation of CBD and the mechanisms involved in its function is required in order to ascertain whether receptor activation could be a treatment alternative for both PD and LID.
Introduction Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. ...Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
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•Mid-IR spectra revealed distinctive features and bands between THC(A) and CBD(A).•FTIR quantification of THC and CBD in Cannabis flowers and extracts was performed.•PLS models using ...2nd derivative of 1800–400 cm−1 spectral region were constructed.•Statistical output points to favorable THC and CBD content prediction capabilities.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most notable Cannabis components with pharmacological activity and their content in the plant flowers and extracts are considered as critical quality parameters. The new Medical Cannabis industry needs to adopt the quality standards of the pharmaceutical industry, however, the variability of phytocannabinoids content in the plant material often exerts an issue in the inconsistency of the finished product quality parameters. Sampling problems and sample representativeness is a major limitation in the end-point testing, particularly when the expected variation of the product quality parameters is high. Therefore, there is an obvious need for the introduction of Process Analytical Technology (PAT) for continuous monitoring of the critical quality parameters throughout the production processes. Infrared spectroscopy is a promising analytical technique that is consistent with the PAT requirements and its implementation depends on the advances in instrumentation and chemometrics that will facilitate the qualitative and quantitative aspects of the technique. Our present work aims in highlighting the potential of mid-infrared (MIR) spectroscopy as PAT in the quantification of the main phytocannabinoids (THC and CBD), considered as critical quality/material parameters in the production of Cannabis plant and extract. A detailed assignment of the bands related to the molecules of interest (THC, CBD) was performed, the spectral features of the decarboxylation of native flowers were identified, and the specified bands for the acid forms (THCA, CBDA) were assigned and thoroughly explained. Further, multivariate models were constructed for the prediction of both THC and CBD content in extract and flower samples from various origins, and their prediction ability was tested on a separate sample set. Savitskzy-Golay smoothing and the second derivative of the native MIR spectra (1800–400 cm−1 region) resulted in best-fit parameters. The PLS models presented satisfactory R2Y and RMSEP of 0.95 and 3.79% for THC, 0.99 and 1.44% for CBD in the Cannabis extract samples, respectively. Similar statistical indicators were noted for the Partial least-squares (PLS) models for THC and CBD prediction of decarboxylated Cannabis flowers (R2Y and RMSEP were 0.99 and 2.32% for THC, 0.99 and 1.33% for CBD respectively). The VIP plots of all models demonstrated that the THC and CBD distinctive band regions bared the highest importance for predicting the content of the molecules of interest in the respected PLS models. The complexity of the sample (plant tissue or plant extract), the variability of the samples regarding their origin and horticultural maturity, as well as the non-uniformity of the plant material and the flower-ATR crystal contact (in the case of Cannabis flowers) were governing the accuracy descriptors. Taking into account the presented results, ATR-MIR should be considered as a promising PAT tool for THC and CBD content estimation, in terms of critical material and quality parameters for Cannabis flowers and extracts.
Various countries and US States have legalized cannabis, and the use of the psychoactive 1 and non-psychoactive cannabinoids is steadily increasing. In this review, we have collated evidence from ...published non-clinical and clinical sources to evaluate the abuse, dependence and associated safety risks of the individual cannabinoids present in cannabis. As context, we also evaluated various synthetic cannabinoids. The evidence shows that delta-9 tetrahydrocannabinol (Δ 9 -THC) and other psychoactive cannabinoids in cannabis have moderate reinforcing effects. Although they rapidly induce pharmacological tolerance, the withdrawal syndrome produced by the psychoactive cannabinoids in cannabis is of moderate severity and lasts from 2 to 6 days. The evidence overwhelmingly shows that non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans. There has been much speculation whether cannabidiol (CBD) influences the psychoactive and potentially harmful effects of Δ 9 -THC. Although most non-clinical and clinical investigations have shown that CBD does not attenuate the CNS effects of Δ 9 -THC or synthetic psychoactive cannabinoids, there is sufficient uncertainty to warrant further research. Based on the analysis, our assessment is cannabis has moderate levels of abuse and dependence risk. While the risks and harms are substantially lower than those posed by many illegal and legal substances of abuse, including tobacco and alcohol, they are far from negligible. In contrast, potent synthetic cannabinoid (CB1/CB2) receptor agonists are more reinforcing and highly intoxicating and pose a substantial risk for abuse and harm. 1 “Psychoactive” is defined as a substance that when taken or administered affects mental processes, e.g., perception, consciousness, cognition or mood and emotions.
This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the ...safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. The systematic search took place in February/2017 and updated in December/2017 using the keywords "epilepsy" or "Dravet" or "Lennox-Gastaut" or "CDKL5" combined with "Cannabis," "cannabinoid," "cannabidiol," or "CBD" resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months). Two thirds of patients reported improvement in the frequency of seizures (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/223, 36%), with statistical significance (
< 0.0001). Nevertheless, when the standard clinical threshold of a "50% reduction or more in the frequency of seizures" was applied, only 39% of the individuals were considered "responders," and there was no difference (
= 0.56) between treatments with CBD-rich extracts (97/255, 38%) and purified CBD (94/223, 42%). Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs. 291/346,
< 0.0001) and severe (23/285 vs. 77/346,
< 0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.
Schizophrenia is a serious mental health disorder that confers one of the highest mortality rates of all psychiatric illnesses. Although the disorder's psychotic symptoms are treatable with ...conventional antipsychotics, they remain incurable. Moreover, medication adherence is poor, and individuals with schizophrenia choose to self-medicate with illicit substances, including cannabis. It is well-established that the delta-9-tetrahydrocannabinol (delta-9-THC) component of cannabis elicits psychotomimetic effects at high doses; worsens schizophrenia-related psychosis; commonly develops into cannabis use disorder in individuals with schizophrenia; and increases the risk of earlier-onset schizophrenia symptoms in those harboring genetic susceptibility. However, individuals with schizophrenia commonly use cannabis and cannabis derivatives such as cannabidiol (CBD). These products seem to alleviate psychotic symptoms and relieve adverse side effects of antipsychotic medications. Therefore, one notion that has gained traction is the potential utility of cannabis-derived cannabidiol (CBD) as adjunct treatment to reduce schizophrenia-associated psychosis and other symptoms. Currently, preclinical and clinical data remain inconclusive. The present review distinguishes the mechanisms underlying schizophrenia-associated vs. cannabis-induced psychosis; reviews the evidence for delta-9-THC-mediated exacerbation vs. CBD-mediated amelioration of schizophrenia-associated psychosis; and describes potential approaches for incorporating CBD into schizophrenia therapeutic regimen in a safe and efficacious manner.
Cannabidiol (CBD) is an active ingredient in marijuana that has demonstrated anti-inflammatory properties. It's therapeutic potential and accessibility has made the product popular. Over the counter ...products (OTC) products have also demonstrated therapeutic potential and have been accessible in public markets for a long time. The objective was to better understand the use of CBD and OTC products amongst singers with varying singing styles.
An anonymous online survey was distributed to 1053 singers via The Research Electronic Data Capture (RED-Cap) program in association with Drexel University. The survey aimed to obtain information regarding singing proficiency, styles, if respondents used CBD/OTC products, reasons for use, perceived effects on the voice due to use of these products, and how informed were they in regards to use of these products.
From 1053 singers, we obtained 144 respondents (response rate of 13.7%). The average age of respondents was 51.8 years; There were 47 males, 93 females, and four who were nonbinary or preferred not to provide their gender. The majority of respondents (63.2%) were professional singers. Primary singing styles included operatic (18.1%), sacred (20.8%), and musical theater (20.1%). Eighty-seven point five percent of respondents reported warming up before singing and 22.9% reported cooling down after singing. Thirteen respondents reported use of a cannabidiol (CBD) product. Information resources for CBD used primarily came from an online website (38.5%). Among the 13 respondents who reported use of CBD products, 46.2% of these respondents did not notice any positive effects and 46.2% reported no negative effects on the voice when using CBD products. Eighty-two respondents (56.9%) reported use of an OTC, supplement, or alternative medicine product. Majority received Information resources from a physician or other healthcare provider (81.7%). The most frequently reported OTC or complimentary medications used were reflux medications, antihistamines, acetaminophen, and NSAIDs. Reduced inflammation, improved voice recovery, improved voice quality, and improved voice endurance were commonly reported positive effects on the voice with OTC/AM use. Vocal strain, hoarseness, and dryness were the most commonly reported negative effects on the voice with OTC/AM use.
Stress, anxiety, or chronic pain was often the primary reason for CBD use amongst singers. The most common OTC medications were used reflux medications, antihistamines, acetaminophen, and NSAIDs.
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•Inexpensive production of trans-isopiperitenol from enantiopure carvone.•Boron trifluoride mediated coupling of olivetol and isopiperitenol.•Robust syntheses of (+)-cannabidiol ...(CBD), (+)-abn-CBD, and (+)-bis-CBD.•First syntheses of (+)-ent-cannabidivarin (CBDV) and (+)-ent-cannabidiphorol (CBDP)•Novel Syntheses of hexyl (CBD-Hex) and octyl (CBD-Oct) CBD-derivatives.
(−)-Cannabidiol (−)-CBD has recently gained prominence as a treatment for neuro-inflammation and other neurodegenerative disorders; interest is also developing in its synthetic enantiomer, (+)-CBD, which has a higher affinity to CB1/CB2 receptors than the natural stereoisomer. We have developed an inexpensive, stereoselective route to access ent-CBD derivatives using (+)-carvone as a starting material. In addition to (+)-CBD, we report the first syntheses of (+)-cannabidivarin, (+)-cannabidiphorol as well as C-6/C-8 homologues.
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