“The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ9-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system. Here, the complexity of the plant-derived and endogenous cannabinoids (eCBs) is discussed, to better appreciate the challenge of: (i) dissecting their mutual interactions; (ii) understanding their impact on human pathophysiology; and (iii) exploiting them for human disease. To this aim, missing pieces to the eCB puzzle must be urgently found, by solving the 3D structures of key components, and interrogating noncanonical modes of regulation and trafficking of these lipid signals.”
Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Untargeted characterization of extracts from Cannabis sativa L. cultivars by gas and liquid chromatography coupled to mass spectrometry in high resolution mode.
“Elucidation of Cannabis composition is required to evaluate the potential of this plant for pharmacological uses, but also for implementation in breeding programs with agronomical purposes. The aim of the present study was to develop a method for untargeted analysis of polar and non-polar Cannabis extracts.
For this purpose, extracts from 17 cultivars of Cannabis sativa L. were analyzed by gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF MS/MS) in high resolution mode.
One hundred sixty-nine compounds were identified in the extracts by searching MS and MS/MS information. Among identified families, there were mainly cannabinoids, terpenoids, lipids and flavonoids, but also some interesting compounds such as amino and organic acids, among others.
Relative contents of terpenoids and cannabinoids in the same cultivars grown in greenhouse and field were compared. Compositional differences in the profile of terpenoids and cannabinoids between both types of grown conditions were found.”
https://www.ncbi.nlm.nih.gov/pubmed/31816756
https://www.sciencedirect.com/science/article/abs/pii/S0039914019310173?via%3Dihub
Cannabis Use in Children With Pantothenate Kinase-Associated Neurodegeneration.
“Pantothenate kinase-associated neurodegeneration is characterized by severe, progressive dystonia. This study aims to describe the reported usage of cannabis products among children with pantothenate kinase-associated neurodegeneration.
METHODS:
A cross-sectional, 37-item survey was distributed in April 2019 to the families of 44 children who participate in a clinical registry of individuals with pantothenate kinase-associated neurodegeneration.
RESULTS:
We received 18 responses (40.9% response rate). Children were a mean of 11.0 (SD 4.3) years old. The 15 respondents with dystonia or spasticity were on a median of 2 tone medications (range 0-9). Seven children had ever used cannabis (38.9%). The most common source of information about cannabis was other parents. Children who had ever used cannabis were on more tone medications, were more likely to have used opiates, were less likely to be able to roll, and less likely to sit comfortably, than children who had never used cannabis. Four children reported moderate or significant improvement in dystonia with cannabis. Other areas reported to be moderate or significantly improved were pain (n = 3), sleep (n = 4), anxiety (n = 3), and behavior (n = 2). Adverse effects included sadness (n = 1), agitation/behavior change (n = 1), and tiredness (n = 1).
CONCLUSION:
Cannabis use was commonly reported among children with pantothenate kinase-associated neurodegeneration whose parents responded to a survey, particularly when many other dystonia treatments had been tried. Physicians should be aware that parents may treat their child with severe, painful dystonia with cannabis. Placebo-controlled studies of products containing cannabidiol and 9-tetrahydrocannabinol are needed for pediatric tone disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/31823681
https://journals.sagepub.com/doi/abs/10.1177/0883073819890516?journalCode=jcna
More evidence of cannabis efficacy in restless legs syndrome.
“Restless legs syndrome (RLS) is one of the most disabling and sometimes painful sensorimotor ailment of the nervous system that has only in recent years become more widely accepted as a clinical disorder with its own distinct features. Usually, symptoms respond well to dopamine agonists, anticonvulsants, or opiates, but still a subset of patients remains refractory to medical therapy and/or reports serious side effects.
Recently, patients’ statement of a remarkable and total remission of RLS symptoms following cannabis use has been reported. Here, we confirm and extend these findings to more patients with RLS.
The antinociceptive effect of marijuana has been documented in many painful neurological conditions, and the potential benefit of cannabis use in patients with refractory RLS should therefore be questioned by robust clinical trials.”
https://www.ncbi.nlm.nih.gov/pubmed/31820197
https://link.springer.com/article/10.1007%2Fs11325-019-01978-1
Characteristics of Dispensary Patients that Limit Alcohol after Initiating Cannabis.
“Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol.
The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters).
Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders).
Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05).
This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.”
https://www.ncbi.nlm.nih.gov/pubmed/31813342
https://www.tandfonline.com/doi/abs/10.1080/02791072.2019.1694199?journalCode=ujpd20
Activation of Cannabinoid Receptors Attenuates Endothelin-1-induced Mitochondrial Dysfunction in Rat Ventricular Myocytes.
“Evidence suggests that activation of the endocannabinoid system offers cardioprotection.
Aberrant energy production by impaired mitochondria purportedly contributes to various aspects of cardiovascular disease. We investigated whether cannabinoid (CB) receptor activation would attenuate mitochondrial dysfunction induced by endothelin-1 (ET1).
Acute exposure to ET1 (4 h) in the presence of palmitate as primary energy substrate induced mitochondrial membrane depolarization, and decreased mitochondrial bioenergetics and expression of genes related to fatty acid oxidation (i.e. peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, a driver of mitochondrial biogenesis, and carnitine palmitoyltransferase (CPT)-1β, facilitator of fatty acid uptake).
A CB1/CB2 dual agonist with limited brain penetration, CB-13, corrected these parameters. AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, mediated the ability of CB-13 to rescue mitochondrial function. In fact, the ability of CB-13 to rescue fatty acid oxidation-related bioenergetics, as well as expression of PGC-1α and CPT-1β, was abolished by pharmacological inhibition of AMPK using compound C and shRNA knockdown of AMPKα1/α2, respectively.
Interventions that target CB/AMPK signaling might represent a novel therapeutic approach to address the multi-factorial problem of cardiovascular disease.”
https://www.ncbi.nlm.nih.gov/pubmed/31815823
https://insights.ovid.com/crossref?an=00005344-900000000-98463
The Cannabinoid Receptor Agonist WIN55,212-2 Ameliorates Hippocampal Neuronal Damage After Chronic Cerebral Hypoperfusion Possibly Through Inhibiting Oxidative Stress and ASK1-p38 Signaling.
“Chronic cerebral hypoperfusion (CCH) is a major contributor to cognitive decline and degenerative processes leading to Alzheimer’s disease, vascular dementia, and aging. However, the delicate mechanism of CCH-induced neuronal damage, and therefore proper treatment, remains unclear.
WIN55,212-2 (WIN) is a nonselective cannabinoid receptor agonist that has been shown to have effects on hippocampal neuron survival. In this study, we investigated the potential roles of WIN, as well as its underlying mechanism in a rat CCH model of bilateral common carotid artery occlusion.
These findings indicated that WIN may be a potential therapeutic agent for ischemic neuronal damage, involving a mechanism associated with the suppression of oxidative stress and ASK1-p38 signaling.”
https://www.ncbi.nlm.nih.gov/pubmed/31808139
https://link.springer.com/article/10.1007%2Fs12640-019-00141-8
Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV.
“Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI).
Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties.
In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age.
METHODS:
Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV-) (18-79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score ≥ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI.
RESULTS:
In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33-0.85) but not among HIV- individuals (P = 0.40). These effects did not vary by age.
CONCLUSIONS:
Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.”
https://www.ncbi.nlm.nih.gov/pubmed/31809361
https://insights.ovid.com/crossref?an=00126334-202001010-00008
An Open-Label Pilot Study Testing the Feasibility of Assessing Total Symptom Burden in Trials of Cannabinoid Medications in Palliative Care.
“There is considerable interest in the use of cannabinoids for symptom control in palliative care, but there is little high-quality evidence to guide clinical practice.
Objectives: Assess the feasibility of using global symptom burden measures to assess response to medicinal cannabis, to determine median tolerated doses of cannabidiol (CBD) and tetrahydrocannabinol (THC), and to document adverse events (AEs).
Design: Prospective two-arm open-label pilot trial of escalating doses of CBD and THC oil.
Setting/Subjects: Participants had advanced cancer and cancer-related symptoms in a palliative and supportive care service in an Australian cancer center.
Measurements: The main outcome measures were the number of participants screened and randomized over the time frame, the number of participants completing days 14 and 28 and providing total symptom distress scores (TSDSs) (measured using the Edmonton Symptom Assessment Scale), and the change from baseline of the TSDS at day 14.
Results: Of the 21 participants enrolled (CBD, n = 16; THC, n = 5), 18 (86%) completed the primary outcome measure at day 14 and 8 completed at day 28. The median maximum tolerated doses were CBD, 300 mg/day (range 100-600 mg); THC, 10 mg/day (range 5-30 mg). Nine of 21 patients (43%) met the definition of response (≥6 point reduction in TSDS). Drowsiness was the most common AE.
Conclusions: Trials of medicinal cannabis in advanced cancer patients undergoing palliative care are feasible. The doses of THC and CBD used in this study were generally well tolerated and the outcome measure of total symptom distress is promising as a measure of overall symptom benefit.”
Long-term benefit from immune modulation and anti-inflammatory treatment in metastatic mesothelioma.
“A 64 year old male heating engineer was investigated for a persistent cough and found to have epithelioid mesothelioma with pleural effusion, lung nodules and increased thoracic lymph nodes. He declined standard of care treatment following his own research and he was enrolled in a named patient programme of IMM-101. He was advised to correct his low vitamin D3 level and to start using anti-inflammatories such as aspirin, bromelain and low dose Naltrexone. At review one year later a CT scan showed no change and he continued on the regimen. Four years after the diagnosis a CT scan showed that there was a modest but definite progression of the left malignant pleural thickening, and a new right-sided effusion, enlargement of several intrathoracic nodes which had been noted on the early scans. The chest wall lump eventually broke down and required local radiotherapy. He then developed abdominal pain and found to have peritoneal disease. Last year he obtained the cannabinoids CBD and THC which slowed down the disease and a CT scan after he had been on this for six months, showed that his disease was fairly stable with marginal progression.”
https://www.ncbi.nlm.nih.gov/pubmed/31788420
“The patient gave his full written consent for this report and is keen that others can benefit from this treatment.”
https://www.sciencedirect.com/science/article/pii/S2213007119303168?via%3Dihub