Cannabis-Based Products in a Neurological Setting: A Clinical and Pharmacokinetic Survey

I suppose you could ask your doctor to get Sativex from the UK off label for your spasticity.

Sativex, a cannabis based spray, was approved in England in 2019 for use in moderate to severe spasticity(only MS) when other treatments haven’t worked.

Currently, Sativex is not approved for any indication in the US, so you are totally screwed unless you are in a legal marijuana state and want to experiment on your own. But you can't, that would only be allowed if prescribed by your doctor. And your doctor will never prescribe marijuana.

 

Cannabis-Based Products in a Neurological Setting: A Clinical and Pharmacokinetic Survey

Susan Mohamed¹, Giovanna Lopane¹, Loredana Sabattini¹, Cinzia Scandellari¹, Diletta Zardi², Vincenzo Donadio¹, Giovanni Rizzo¹, Alessandro Perrone¹, Alessandra Lugaresi^1,2† and Manuela Contin^1,2*†

• ¹IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
• ²Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

Background and Aim: Limited data are available in clinical settings on the pharmacokinetics of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). We investigated the use of cannabis-based products in neurological practice, monitoring patients' steady-state cannabinoids (CBs) plasma concentrations matched with different preparations.

Methods: This was a prospective, single-center, observational study. Patients underwent venous blood withdrawal before the CBs' morning dose and then 2.5 h post-dosing. Spasticity or pain were patient self-assessed by the Numeric Rating Scale (NRS) before the morning CB's administration and 2.5 h post-dosing.

Results: Thirty-three patients were enrolled. Main indications for CBs were spasticity and chronic pain. Sixteen patients were treated with oromucosal spray formulation Sativex^® and 17 with oil-based solutions. Both CBs trough plasma concentrations were ≤ limit of detection (0.1 ng/ml) in 45% of patients. Intrasubject CB's plasma levels significantly increased over baseline values in patients treated with Bediol^® oil (p < 0.05) and Sativex^® (p < 0.01). Post-dosing CB's bioavailability did not significantly differ between oral oil and oromucosal spray. NRS scores decreased (p < 0.01), matching the increase (p < 0.01) in CB's plasma concentrations.

Conclusion: This is the first study investigating CB's plasma concentrations of oral and oromucosal preparations in real-world neurological practice. Findings of similar bioavailability for both CBD and THC after galenic oil compared with oromucosal spray dosing may be clinically relevant and deserve additional research in larger cohorts.

Introduction

The cannabis plant contains several substances, such as more than one hundred cannabinoids (CBs) (1). There is great interest in the use of cannabis for the management of many diseases and symptoms (2) and the attention has been focused in particular on the two CBs, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) (3).

Two types of CB receptors have been identified, CB1 and CB2, which are parts of the human endocannabinoid system, involved in various functions, such as muscle spasticity, analgesic activity, anticonvulsant properties, vasodilatory and hypotensive action, and appetite (3).

THC is a partial agonist of CB1 and CB2 receptors. The main pharmacological effects of THC are psychoactivity, analgesia, muscle relaxation, anti-vomiting, and stimulation of appetite (3). Muscle relaxant effects are also recognized for hyper-reflexic bladder (4, 5).

Cannabidiol does not have a direct effect on the CB1 or CB2 receptors responsible for cannabis psychoactivity but it has been shown to have a negative allosteric activity on CB1 (6). From experimental models of epilepsies, different CBD mechanisms have emerged, such as antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and interactions with voltage-gated sodium and potassium channels (7). Other mechanisms associated with anti-inflammatory pathways include direct agonistic activity on serotonin 1A and adenosine A2A receptors (8). The main pharmacological effects of CBD are antiseizure, muscle relaxant, anxiolytic, and anti-inflammatory (1).

In the literature, several works have examined the efficacy and safety of CB's preparations in the treatment of a series of symptoms associated with neurological diseases, such as multiple sclerosis (MS), epilepsies, Huntington's disease, Parkinson's disease, cervical dystonia, and Tourette's syndrome. These applications were reviewed by an ad hoc guideline development subcommittee of the American Academy of Neurology (9). Chronic pain is another field of use of therapeutic cannabis, although few rigorous studies have evaluated its effectiveness (10).

Available data on CB's safety from clinical trials and real-world experience show that the most common adverse effects (AEs) associated with THC are dizziness, drowsiness, dry mouth, nausea/vomiting, impairment in cognitive function (perception disorders, euphoria, and confusion) and psychomotor skills, balance, and coordination problems (11). Studies on recreational cannabis have suggested a link between early, frequent use of high potency THC, and earlier onset of psychosis in subjects with a personal or family history of schizophrenia or psychotic disorders (12). CBD's common AEs include diarrhea, somnolence, pyrexia, decreased appetite, vomiting, and upper respiratory tract infection (11).

In Italy, two cannabis medicinal products are authorized: one based on THC and CBD, in the approximate 1:1 dose ratio (2.7 mg THC and 2.5 mg for CBD), in a spray for oral mucosa (Sativex^®, GW Pharmaceuticals, UK), indicated to relieve symptoms in adult patients who suffer from moderate to severe spasticity due to MS. The other, marketed from the end of June 2021, is based on purified plant-based CBD, in an oil oral formulation (Epidiolex, GW Pharmaceuticals, UK), indicated as an adjunct treatment of seizures associated with two rare, severe forms of epilepsy with childhood onset, the Lennox-Gastaut and Dravet syndromes. Furthermore, there are several available cannabis galenical preparations (i.e., oil extracts, decoctions) characterized by different percentages of THC and CBD (Supplementary Table 1), which can be prescribed by physicians to users registered on the Italian Ministry of Health database (13). Eligible indications of medical cannabis include the management of the chronic pain associated with MS and spinal cord injury, the control of nausea and vomiting due to chemotherapy, radiotherapy, or HIV therapy, the handling of appetite loss in oncologic and HIV-positive patients. Medical cannabis is also indicated for its appetite stimulant effect in cachexia and anorexia, its hypotensive effect in glaucoma, and as antispasmodic in Tourette's syndrome (14).

Despite the substantial number of published studies, data on the pharmacokinetics of THC and CBD are limited (15, 16). In particular, the pharmacokinetics of CBs from oral galenical preparations has not been extensively studied in clinical settings (17). CB's posological protocols for physicians are missing (14), thus, currently the management of dosing is largely empirical, based on a balance between the desired therapeutic effects and the prevention of the adverse ones. Knowledge of CB's pharmacokinetics from different available formulations could help the prescribers in optimizing therapeutic regimens.

The purpose of this study was to investigate the use of cannabis-based products at the Institute of Neurological Sciences of Bologna (ISNB), such as indications, type of patients treated, formulations, dosages, evidence of efficacy, and AEs, and to monitor steady-state CB's plasma concentrations matched with different cannabis-based products.

More at link.