Dataset Information

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (?⁹-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

ABSTRACT: Marijuana is one of the most commonly used illicit recreational drugs and is widely used for medicinal purposes. The psychoactive ingredient in marijuana is ?⁹-tetrahydrocannabinol (?⁹-THC), whereas the major non-psychoactive ingredient is cannabidiol (CBD). Here, we exposed zebrafish embryos to ?⁹-THC or CBD for 5?hours during the critical stage of development known as gastrulation. Embryos were allowed to develop normally and were examined at 2 and 5 days post fertilization. THC and CBD treated embryos exhibited reduced heart rates, axial malformations and shorter trunks. Cannabinoid treatment altered synaptic activity at neuromuscular junctions (NMJs), and fluorescent labelling of primary and secondary motor neurons indicated a change in branching patterns and a reduction in the number of axonal branches in the trunk musculature. Furthermore, there were alterations in the ?-bungarotoxin labelling of nicotinic acetylcholine receptors at NMJs. Locomotion studies show that larvae exposed to THC or CBD during gastrulation exhibited drastic reductions in the number of C-start escape responses to sound stimuli, but not to touch stimuli. Together these findings indicate that zebrafish embryos exposed to ?⁹-THC or CBD during the brief but critical period of gastrulation exhibited alterations in heart rate, motor neuronal morphology, synaptic activity at the NMJ and locomotor responses to sound.

SUBMITTER: Ahmed KT

PROVIDER: S-EPMC6043604 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (∆9-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

Ahmed Kazi T KT Amin Md Ruhul MR Shah Parv P Ali Declan W DW

Scientific reports 20180712 1

Marijuana is one of the most commonly used illicit recreational drugs and is widely used for medicinal purposes. The psychoactive ingredient in marijuana is ∆9-tetrahydrocannabinol (∆9-THC), whereas the major non-psychoactive ingredient is cannabidiol (CBD). Here, we exposed zebrafish embryos to ∆9-THC or CBD for 5 hours during the critical stage of development known as gastrulation. Embryos were allowed to develop normally and were examined at 2 and 5 days post ...[more]

PMID: 30002406

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Project description:Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic ? 9-tetrahydrocannabinol (? 9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual ? 9-THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 67 food products of the German market (mostly CBD oils) confirmed this hypothesis: 17 products (25%) contained ? 9-THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of ? 9-THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe ? 9-THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.

Project description:BACKGROUND: Significant interest has emerged in the therapeutic and interactive effects of different cannabinoids. Cannabidiol (CBD) has been shown to have anxiolytic and antipsychotic effects with high doses administered orally. We report a series of studies conducted to determine the vaporisation efficiency of high doses of CBD, alone and in combination with ?9-tetrahydrocannabinol (THC), to achieve faster onset effects in experimental and clinical trials and emulate smoked cannabis. METHODS: Purified THC and CBD (40 mg/ml and 100 mg/ml respectively) were loaded onto a liquid absorbing pad in a Volcano vaporiser, vaporised and the vapours quantitatively analysed. Preliminary studies determined 200 mg CBD to be the highest dose effectively vaporised at 230 ° C, yielding an availability of approximately 40% in the vapour phase. Six confirmatory studies examined the quantity of each compound delivered when 200 mg or 4 mg CBD was loaded together with 8 mg of THC. RESULTS: THC showed 55% availability when vaporised alone or with low dose CBD, while large variation in the availability of high dose CBD impacted upon the availability of THC when co-administered, with each compound affecting the vaporisation efficiency of the other in a dynamic and dose-dependent manner. We describe optimised protocols that enable delivery of 160 mg CBD through vaporisation. CONCLUSIONS: While THC administration by vaporisation is increasingly adopted in experimental studies, often with oral predosing with CBD to examine interactive effects, no studies to date have reported the administration of CBD by vaporisation. We report the detailed methodology aimed at optimising the efficiency of delivery of therapeutic doses of CBD, alone and in combination with THC, by vaporisation. These protocols provide a technical advance that may inform methodology for clinical trials in humans, especially for examining interactions between THC and CBD and for therapeutic applications of CBD. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24109245.

Project description:BackgroundTreatment of spasticity poses a major challenge in amyotrophic lateral sclerosis (ALS) patient management. Delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (THC:CBD), approved for the treatment of spasticity in multiple sclerosis, serves as a complementary off-label treatment option in ALS-related spasticity. However, few structured data are available on THC:CBD in the treatment of spasticity in ALS.MethodA retrospective mono-centric cohort study was realised in 32 patients that meet the following criteria: 1) diagnosis of ALS, 2) ALS-related spasticity; 3) treatment with THC:CBD. Spasticity was rated using the Numeric Rating Scale (NRS). Patient's experience with THC:CBD was assessed using the net promoter score (NPS) and treatment satisfaction questionnaire for medication (TSMQ-9) as captured through telephone survey or online assessment.ResultsThe mean dose THC:CBD were 5.5 daily actuations (range?<?1 to 20). Three subgroups of patients were identified: 1) high-dose daily use (? 7 daily actuations, 34%, n?=?11), 2) low-dose daily use (<?7 daily actuations, 50%, n?=?16), 3) infrequent use (<?1 daily actuation, 16%, n?=?5). Overall NPS was +?4.9 (values above 0 express a positive recommendation to fellow patients). Remarkably, patients with moderate to severe spasticity (NRS???4) reported a high recommendation rate (NPS: +?29) in contrast to patients with mild spasticity (NRS?<?4; NPS: -?44). For the three main domains of TSQM-9 high mean satisfaction levels were found (maximum value 100): effectiveness 70.5 (±22.3), convenience 76.6 (±23.3) and global satisfaction 75.0 (±24.7).ConclusionTHC:CBD is used in a wide dose range suggesting that the drug was applied on the basis of individual patients' needs and preferences. Contributing to this notion, moderate to severe spasticity was associated with an elevated number of daily THC:CBD actuations and stronger recommendation rate (NPS) as compared to patients with mild spasticity. Overall, treatment satisfaction (TSQM-9) was high. The results suggest that THC:CBD may serve as a valuable addition in the spectrum of symptomatic therapy in ALS. However, prospective studies and head-to-head comparisons to other spasticity medications are of interest to further explore the effectiveness of THC:CBD in the management of spasticity, and other ALS-related symptoms.

Dataset Information

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (?⁹-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

Publications

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (∆<sup>9</sup>-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Dataset Information

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (?9-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

Publications

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (∆<sup>9</sup>-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (?⁹-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation.