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review of the neurological benefits of phytocannabinoids

Conclusions: In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.

Results: Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids.

Methods: In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts.

Conflict of interest statement

Keywords: Cannabidiol; delta-9-tetrahydrocannabinol; endocannabinoid system; neurological disease; phytocannabinoids.

Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS.

The Authors report the following conflicts: University of Pittsburgh Medical Center – Employer, National Football League – Medical Consultant – Non-paid consultant, Pittsburgh Steelers Football Club – Medical Consultant – Non-paid consultant, World Wrestling Entertainment Corporation – Paid Consultant, ImPACT Applications, INC (Immediate Post Concussion Assessment and Cognitive Testing) – Shareholder, Board Member, CV Sciences – Shareholder.

Before we discuss the medicinal properties of the chemical, I want to provide you with a bit of background on what exactly CBD is. Cannabidiol is a chemical compound found in cannabis. While it does not produce an altered state of mind like THC, the active ingredient in cannabis, it has been speculated to have many healing properties (Grinspoon, 2018). CBD is thought to bind to CB2 receptors throughout the nervous system. The CB2 receptor is heavily expressed in immune system cells and is thought to play a role in neuroinflammation (Maroon & Bost, 2018).

In the past 10 years cannabidiol or CBD has become a staple in what seems like every industry imaginable. From CBD oil infused pillows to CBD toothpicks, you can’t walk 10 feet without finding some new, eclectic CBD product. You have likely heard of the innumerable positive effects of CBD, but which ones are true and which ones are utter nonsense? Today we are going to break down the scientifically proven effects of cannabidiol!

In recent years, there has been an explosion of research surrounding the therapeutic effects of CBD. The data suggests that CBD:

Bobby Moynihan

In the past 10 years cannabidiol or CBD has become a staple in what seems like every.

While there are many studies touting the positive effects of CBD, more research should be conducted to further corroborate the existing data. The only FDA approved treatment involving the use of CBD is in the treatment of several childhood epileptic disorders. While CBD seems to have a low side-effect profile, due to the novelty of CBD research there is not a large swath of data on all of the potential drug interactions. Though CBD has a lot of potential for therapeutic use, it is important to keep this risk in-mind!

Cannabinoid receptor pharmacology began in the late 1960s when Δ9-THC was isolated and synthesized and found to be the primary psychoactive constituent of marijuana.[40,80,81,105] The discovery in the early 1990s of specific membrane receptors for Δ9-THC led to the identification of endogenous signaling system, now known as the endocannabinoid system (ECS). Shortly thereafter, the endogenous cannabinoids, N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), were identified. The ECS consists of two major types of endogenous G protein-coupled cannabinoid receptors (CB1 and CB2) located in the mammalian brain and throughout the central and peripheral nervous systems, including tissues associated with the immune system. CB1 and CB2 receptors can also co-exist in a variety of concentrations in the same locations.[86] Both phytocannabinoids and endogenous cannabinoids function as retrograde messengers that provide feedback inhibition of both excitatory and inhibitory transmission in brain through the activation of presynaptic CB1 receptors. Manipulations of endocannabinoid degradative enzymes, CB1 and CB2 receptors, and their endogenous ligands have shown promise in modulating numerous processes associated with neurodegenerative diseases, cancer, epilepsy, and traumatic brain injury [ Table 1 ]. In addition, the ECS is known to influence neuroplasticity, apoptosis, excitotoxicity, neuroinflammation, and cerebrovascular breakdown associated with stroke and trauma.[105]

Endogenous cannabinoids appear to affect the initiation, propagation, and spread of seizures. Studies have identified defects in the ECS in some patients with refractory seizure disorders, specifically having low levels of anandamide and reduced numbers of CB1 receptors in CSF and tissue biopsy.[97] Additionally, the ECS is strongly activated by seizures, and the upregulation of CB1 receptor activity has antiseizure effects.[27]

Discovery of the endocannabinoid system

Experiments with Δ9-THC have demonstrated a rebound hyperexcitability in the CNS in mice, with enhanced neuronal excitability and increased sensitivity to convulsions and has not been used on most trials of intractable epilepsy. CBD, however, produces antiepileptiform and anticonvulsant effects in both in vitro and in vivo models.[64,51,61,62,63,85]

Despite the preclinical data by GW Pharmaceutical and anecdotal reports on the efficacy of cannabis in the treatment of epilepsy, a 2014 Cochrane review concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy.” This report noted this conclusion was mostly due to the lack of adequate data from randomized, controlled trials of Δ9-THC, CBD, or any other cannabinoid in combination.[28,38,43,83]

In rats lesioned with 3-nitropropionic acid, a toxin inhibitor of the mitochondrial citric acid cycle resulting in a progressive locomotor deterioration resembling that of HD patients, CBD reduces rat striatal atrophy in a manner independent of the activation of cannabinoid adenosine A2A receptors.[100] In contrast, CBD alone did not provide protection in rats lesioned with malonate.[99] A clinical study from 1991 using 15 subjects with HD reported an average daily dose of CBD of 10 mg/kg/day per patient for 6 weeks was reported as safe but did not result on any significant symptom relief.[51] The phytocannabinoid-based medicine Sativex®, a 1:1 combination of CBD and Δ9-THC, has produced neuroprotective effects through a CB1- and CB2-mediated mechanism in a model of HD.[115]