Cannabinoids in neurology – Brazilian Academy of Neurology.

GENERAL ASPECTS

Recently the use of cannabidiol was released to prescribing physicians in the State of São Paulo, at Cremesp (Regional Council of Medicine of the State of São Paulo) on 9 October 2014. ANVISA has released its medicinal use for import into various cases; It requires the prescription and medical report and disclaimer. Increasingly, the therapeutic use of cannabinoids have been discussed. The Brazilian Academy of Neurology through its Scientific Departments took his position according to the scientific evidence on the use of cannabinoids in proper neurological diseases.
The cannabinoids are more exuberant Δ9-tetrahydrocannabinol (THC), which has psychoactive properties and cannabidiol (CBD) that has psychoactive properties. There CNS endocannabinoids, two most abundant types: 2-arachydonoyl Glyc erol and the n-arachidonoyl ethanolamide. They are released in response to excitatory synaptic activity, being synthesized in the body and dendrites of neurons in response to the increase in intracellular calcium concentration. They inhibit the release of neurotransmitters in the final pathway GABAergic terminals and to a lesser extent, glutamate. They act on several mechanisms of plasticity short and long-term inhibitory and excitatory synapses. Several brain areas are rich in CB1 receptors, such as the frontal cortex, basal ganglia, cerebellum and cerebral limbic region. By these mechanisms may act in several neurological ^{1, 2, 3, 4.}

Cognitive Effects

The use of cannabis in inhaled form, by healthy individuals, is associated with worse cognitive performance, either acute or chronic. The suspension of its use partially reverses this fall, without normalizing. Few studies have assessed the effect on cognition of cannabis use in inhaled form in patients with neurological disease. MS patients who used cannabis inhaled form, be it recreational or therapeutic purpose, showed worse cognitive performance in information processing speed test, working memory, executive functions and visuospatial processing ^1. The use of cannabidiol does not seem to be related to cognitive decline, however, few studies would evaluate its use in the elderly ^5.

Cannabinoids IN EPILEPSY

The CBD has recognized antiepileptic effect, however, with mechanism of action, long-term safety, pharmacokinetics and interactions with other drugs, still unclear. The methodologically well conducted clinical trials are limited, as there are legal restrictions on the use of medicines derived from cannabis, although the CBD does not have psychoactive properties.
Dr. Devinsky, at New York University School of Medicine has been authorized by the Federal Drug Administration(FDA) to conduct an open study with a product containing 98% of CBD whose commercial name is Epidiolexmanufactured by GW Pharmace uticals. The daily dose was gradually increased to a maximum of 25 mg / kg / day associated with the medications the patient already used. Results from the first 23 patients, whose average age was 10 years, showed that 39% of patients had a reduction of 50% of its crises. Obtained total control of seizures only 3 of the 9 patients with Dravet’s syndrome (a type of very severe childhood epilepsy) and 1 of 14 patients with other forms of epilepsy. The most common side effects were drowsiness, fatigue, loss or weight gain, diarrhea and increased or decreased appetite. All patients received more than one antiepileptic drug. The preliminary results showed a 50% reduction of seizures in 40% of patients. This result does not differ from the results available in the literature more than 20 antiepileptic drugs available on the market.
Populations exposed to the CBD are composed of heterogeneous patients with epilepsy syndromes that have not responded to any other drug, or had serious side effects from the medications available in the market. In this scenario, a compound that has any beneficial effect becomes potentially useful.
The scientific data available so far lead to the conclusion that cannabidiol can play an important role in the treatment of very difficult epilepsies, in specific cases, not yet scientifically defined.
We emphasize that cannabidiol have applicability within the scene of intractable epilepsies, very difficult to control, possibly with excellent response in some cases, other reasonable response and no response in some, as observed with the use of other drugs. The safety and efficacy of the CBD need to be better established by well-conducted studies, since available data in the literature do not meet the scientific criteria required for such a compound is used as indiscriminately drug in epilepsy.

Cannabinoids in MULTIPLE SCLEROSIS

The use of cannabis in multiple sclerosis (MS) is often discussed in the symptomatic and preventive treatment.Care should be taken as the indication of the use of cannabinoids in oral form in MS, because their adverse effects can be exacerbated due to the inherent characteristics of the disease. Symptoms such as cognitive impairment, fatigue and mood changes, which can range from depression to suicide ideation, must be evaluated before the indication of these substances in MS. The naxibimol is a commercial preparation used in some countries with specific indication for spasticity in MS. Contain THC and CBD in a ratio of 1: 1, use of oro-buccal and exclusively used at the maximum dose of up to 12 puffs a day. There are no consistent studies to therapeutic indication marijuana in the form of cigarettes in any of the symptoms of MS. There are studies class I, II and III for oral preparations and naxibimols for some of the symptoms of MS.
For the treatment of spasticity: Naxibimols studies showed improvement in self-assessment scales in six weeks, although improvements were not observed in objective scales for spasticity. Its long-term effectiveness has not been confirmed. The extract of cannabis and oral THC also proved effective only on self-assessment scales in use for up to 15 weeks, but after a year the results indicated an improvement also in the objective scales of measurement of spasticity. These results suggest that this therapeutic option can be considered in patients with MS, although there are no safety studies used for long periods ^6.
In neuropathic or central pain, studies were conducted over short periods, with variable efficacy. The naxibimols, the prepared with THC / CBD and cannabis extract showed conflicting results, and although it is not possible to conclude definitively as to its effectiveness, the data suggest that this may be a therapeutic option for patients who have not responded to conventional treatments ^{7, 8, 9, 10, 11.}
In the treatment of tremor and bladder dysfunction, use of oral preparations naxibimols or THC, CBD or THC / CBD was shown to be ineffective at this time there is no indication for its use in the relief of this symptom.
In conclusion, the naxibimol can be used in spasticity and pain of MS, since exhausted all other therapeutic possibilities, always taking risks and benefits of your statement.

Cannabinoids in Parkinson’s Disease AND OTHER MOVEMENT DISORDERS

The American Academy of Neurology (AAN) has recently published a systematic review on the efficacy and safety of the therapeutic use of marijuana and its derivatives in the treatment of neurological diseases ^10.
This extensive work of AAN can see that there are few quality studies available in the literature to have a final conclusion about the therapeutic use of derivatives of cannabis in patients with movement disorders. It should be considered that the risk of serious psychopathological effects can reach 1%. This will depend undoubtedly the proportion of THC present in the treatment, but somehow there are no reports of serious side effects. Cannabis extracts do not improve dyskinesias induced by levodopa in patients with Parkinson’s disease (PD).
Recently, preliminary studies using pure CBD in the treatment of patients with PD revealed a positive effect on psychotic symptoms, sleep and quality of life of patients ^11. The CBD could have a therapeutic effect on the symptoms of REM sleep behavior disorder ^12.
In conclusion, despite the absence of sufficient evidence to indicate the use of derivatives of cannabis for patients with movement disorders, there is evidence that the use of plant extracts and especially CBD can help minimize non-motor symptoms of PD as: psychosis, sleep disorders, pain, perhaps urgency, and also promote a general improvement in the quality of life of patients. The therapeutic use without precise indication would only be indicated in cases of movement disorders in which conventional treatments available have failed, and the patient’s quality of life is severely compromised. It is likely that the use of pure CBD and cannabis extracts with low THC content are more efficient and less likely to cause side effects ^12.

Cannabinoids NO PAIN TREATMENT OF NEUROPATHIC

Three studies evaluated the efficacy of marijuana in treating neuropathic pain. In one spray form has been used as an adjuvant analgesic in the treatment of central pain in patients with multiple sclerosis. Another study used inhaled form, in patients with post-traumatic neuropathic pain and post-surgical, with improvement in pain intensity ^13. Finally, Ellis et al. observed improvement of neuropathic pain in patients with HIV ^14.
Because it is a treatment of SFBR type (Simple, Easy, Cheap and Rational) as opposed to expensive, toxic and costly treatments may be an option in cases of refractory pain in therapeutic failures or insufficient efficacy. For its systematic use would be most appropriate amount of studies ^15.

Cannabinoids in HEADACHE

There are no recent studies on its use in headache. Although some diseases related to pain of head segment respond to the use of s cannabinoid, as in orofacial neuropathic pain (trigeminal neuralgia, the burning mouth syndrome and persistent orofacial pain) and its effect on central pain system (trigeminal system and gray matter periaqueductal) have intense intersection with painful pathways involved in headaches, especially migraine, we can not say, the lack of specific studies that may be suitable for treatment ^{16, 17, 18.}

FINAL CONSIDERATIONS

There appear to be evidence of beneficial effects of cannabinoids on changes in the central and peripheral nervous system, however, long-term studies are needed with larger numbers of patients, with efficacy measured by objective instruments and their long-term use is not yet known. The use of cannabidiol is indicated in the treatment failure of treatments already established or when they have insufficient efficacy. The use of cannabis recreationally is contraindicated for ABN.
(Translated by Google)