Cannabinoids in the nervous system: how do they work?

There are several studies that prove the effectiveness of a treatment using this natural substance, extracted from Cannabis Sativa.

Now, the time has come to understand a little more about and know the main advantages of this therapy. Follow the reading with us.

What are cannabinoids in the nervous system?

The term cannabinoids refers to a heterogeneous group of compounds classified into three main groups: endogenous, synthetic and phytocannabinoids.

These substances act on the endocannabinoid system, which in the central nervous system (CNS) comprises mainly the cannabinoid receptors CB1 and CB2.

Not counting its endogenous agonists, the endocannabinoids (EC), such as: anandamide (AEA), 2-arachidonoilglycerol (2-AG) and protein complexes responsible for its absorption, synthesis and degradation.

Because of this, there is a growing interest in studies on the neurological action and therapeutic use of cannabinoids; and an excellent theoretical basis for its use. Several works have been published, with promising results in the field of neurology.

The potential therapeutic actions of delta-9-THC and CBD cannabinoids are based on their activity as an anti-inflammatory, anticonvulsant, analgesic, and antiemetic.

Results from laboratory and human studies suggest positive effects as new experimental agents for CNS diseases, including schizophrenia and epilepsy.

Due to lipophilicity, that is, the ability of a chemical compound to be dissolved in fats, vegetable oils, lipids in general, THC and CBD, plus their neurological actions, they are natural candidates as new therapeutic approaches for the treatment of these pathologies.

Below are therapeutic possibilities and neurological pathologies with the use of CBD.

Cannabinoid and epilepsy studies

The first records of the use of cannabinoids in the nervous system for medicinal purposes appear in approximately 2700 BC in China. However, global interest in medicinal use in epilepsy has gained momentum in the 21st century.

In 2017, Devinsky et al. conducted a double-blind, placebo-controlled, randomized clinical trial to assess the efficacy of Epidiolex for seizures in 120 children and adult patients with Dravet syndrome.

This is a rare, progressive, and disabling genetic problem. It may also be known by some professionals as childhood severe myoclonic epilepsy.

Among the main points that stand out in the syndrome are cognitive deficits, motor problems and characteristics of autism.

In another double-blind placebo-controlled study, Thiele et al. evaluated the efficacy of Epidiolex for atonic seizures in 225 patients with Lennox-Gastaut syndrome.

It is an alteration in the central nervous system that appears in childhood and corresponds to a part of epilepsy scenarios among children aged 1 to 8 years. Its main features range from progressive mental retardation to multiple types of seizures

This study showed a reduction of at least 50% in seizure frequency among patients who were primarily in the CBD group, 43%, compared to 27% in the placebo group.

The recommended dose of CBD for the treatment of refractory epilepsy was 10 to 25 mg/kg/day (about 200 to 300 mg/day).

Thus, the interaction of CBD with anticonvulsant medications seems to be common in patients with epilepsy, especially with clobazam and valproate. Importantly, these two drugs can influence cannabinoid treatment.

Can Cannabinoids Work in Multiple Sclerosis?

The use of cannabinoids in the nervous system for the treatment of multiple sclerosis began as a complementary symptomatic treatment, especially for those symptoms not fully controlled by conventional therapies.

Thus, the THC/CBD combination therapy, at a ratio of 1:1, exclusively for oral use and used at a maximum dose of up to 12 puffs per day, combined with nabiximol (Sativex), showed an improvement of more than 20% in the spasticity parameters after four weeks of use compared to placebo.

This treatment modality was approved by the Food and Drug Administration (FDA) for the treatment of severe and refractory spasticity in patients with multiple sclerosis, contributing to the therapeutic arsenal in the pathology.

In neuropathic or central pain, nabiximols showed improvement in pain compared to placebo in patients with multiple sclerosis.

Furthermore, positive results in the efficacy of chronic neuropathic pain control in the association of nabilone with gabapentin were also found.

Chronic pain affects 30% of the world population, according to data presented by the World Health Organization (WHO) in general and is the main cause of years lived with disability from all diseases worldwide.

There are several chronic pain syndromes, grouped according to the primary pathophysiological mechanism related to their occurrence.

Often, patients with chronic pain may seek prescription cannabinoids to relieve symptoms that are not directly related to pain, but rather to improve sleep, anxiety, concentration, mood, well-being, or muscle relaxation.

The identification of this primary objective is essential to analyze whether cannabinoids would be the best treatment available for the demand and, thus, guide patients as to the most appropriate form of pharmacological or non-pharmacological treatment.

This “symptom targeting” is also essential for monitoring the effects of cannabinoids if they are initiated.

The use of CBD can be isolated, or in association with THC, which is more frequently titled, given the medication potential psychotropic effects.

Cannabinoids and neuromuscular diseases

The role of the endocannabinoid system (ECS) in muscle physiology was initially identified in animal models as responsible for functions related to energy expenditure and glucose uptake.

In this sense, it is possible to infer that the endocannabinoid system possibly influences the pathophysiology of several myopathies, especially muscular dystrophies.

Studies with an animal model of Duchenne muscular dystrophy (DMD) treated with phytocannabinoid agents, CBD, cannabivarin (CBDV) and tetrahydrocannabivarin (THCV), showed a sustained improvement in motor performance in treated animals when compared to controls.

Evidence from animal models has shown that CB2 receptors play a role in the muscle inflammatory response during the course of muscle repair.

Its activation attenuates the inflammatory response and favors the antifibrotic / profibrotic balance in the muscle repair process, while its blockage results in the opposite effects.

It is noteworthy that scientific advances and new studies to be conducted, especially randomized placebo-controlled clinical trials, may provide even more data on the use of cannabinoids in neurology, reinforcing the positive data already published on the benefit of this therapy in various pathologies.

Throughout the text, you can learn about how cannabinoids act on our endocannabinoid system and help our body, especially when faced with neurological problems and diseases.

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Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020 Jan;16(1):9-29.

Devinsky O, Cross JH, Wright S. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 Aug;377(7):699-700.

Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials. Epilepsia 2020 Jun;61(6):1082-9.

Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: a systematic review and meta-analysis. JAMA Netw Open.

Pharmacological actions and potential therapeutic use of cannabinoids in Duchenne’s muscular dystrophy. Muscular Dystrophies, Kunihiro Sakuma. IntechOpen. 2019.