I'm currently trying to get Epidiolex off-label for my akathisia. High CBD cannabis has been a salve for me.
I used a cbd isolate and noticed benefit from as little as 12.5 mg cbd daily, however my akathisia is not the worst it's been in recent years. Benefits seemed to build over time. Someone with more serious akathisia might do better with more, I can't say from experience though when it comes to severe akathisia. I discontinued use due to it aggravating tachycardia and arrhythmia, I've read reports of this occurring with cbd use in a few other people as well.
What ratio do you use and how much do you take?
Just wanted to post a link to this study that found that Cannabidiol (such as in CBD oil) reduces movement disorders. I've found it reduces the effects of my akathisia more potently than anything else I've tried. Hopefully this helps someone else out there too.
Hopefully there aren't any restrictions for its off label use where you are, I wish you good luck with that. I can't remember the name of the drug but there is currently another mainstream brand of purified CBD currently in trials somewhere (I think a European country) for the treatment of neurodegenerative diseases and Schizophrenia, I hope that will open further people up to treatment options in the near future. This is also good news as I believe these drugs such as Epidiolex are purified CBD without any trace amounts of THC in them as you'd find in CBD oils, even in CBD isolates, so people can take drug tests without running into issues. It's really sad that currently people in many places around the world with issues such as with mental health or akathisia can be made well enough to get a job thanks to a CBD oil but then they could fail the drug test in the job application process.
In an in vitro study, CBD increased the viability of cells treated with the neurotoxin N-methyl-4-phenylpyrimidine (MPP+), and prevented the MPP+-induced increase in caspase-3 activation and decrease in levels of nerve growth factor (NGF) (Santos et al., 2015). CBD treatment was also able to induce cell differentiation even in the presence of MPP+, an effect that depends on trkA receptors (Santos et al., 2015). MPP+ is a product of oxidation of MPTP that inhibits complex I of the respiratory chain in dopaminergic neurons, causing a rapid neuronal death (Schapira et al., 1990; Meredith et al., 2008).
In spite of the pre-clinical encouraging results with Sativex, a pilot trial with 25 HD patients treated with Sativex for 12 weeks failed to detect improvement in symptoms or molecular changes on biomarkers (López-Sendón Moreno et al., 2016). Nonetheless, Sativex did not induce severe adverse effects or clinical worsening (López-Sendón Moreno et al., 2016). The authors suggest that future studies, with higher doses and/or longer treatment periods, are in need. More recently, one study described the results of administering cannabinoid drugs to 7 patients (2 of them were treated with Sativex; the others received dronabinol or nabilone, agonists of the cannabinoid receptors): patients displayed improvement on UHDRS motor score and dystonia subscore (Saft et al., 2018).
With respect to cognitive effects, studies report that CBD does not impair cognition, being even able to improve it in some conditions. Pre-clinical data show that CBD restores the deficit in the novel object recognition task in mice treated with MK-801 (a protocol used to model schizophrenia) (Gomes et al., 2015), in rats submitted to neonatal iron overload (Fagherazzi et al., 2012), in a transgenic mice model for Alzheimer’s disease (Cheng et al., 2014), and in a mice model for cerebral malaria (Campos et al., 2015). CBD also reverses impaired social recognition in a murine model for Alzheimer’s disease (Cheng et al., 2014) and restores the deficits in the Morris water maze—a task that evaluates spatial learning—in rodent models for Alzheimer’s disease (Martín-Moreno et al., 2011), brain ischemia (Schiavon et al., 2014) and cerebral malaria (Campos et al., 2015). In addition, studies demonstrate that CBD per se does not modify animals’ performance in cognitive tasks (Osborne et al., 2017; Myers et al., 2018) and does not induce withdrawal after prolonged treatment (Myers et al., 2018). In accordance, in one recent clinical trial using CBD as an adjunctive therapy for schizophrenia, CBD group displayed greater cognitive improvement (assessed by BACS—Brief Assessment of Cognition in Schizophrenia), although it fell short of significance (McGuire et al., 2018). CBD also improves facial emotion recognition in cannabis users (Hindocha et al., 2015).
CBD has several molecular targets, and new ones are currently being uncovered. CBD antagonizes the action of CB1 and CB2 receptors agonists, and is suggested to act as an inverse agonist of these receptors (Pertwee, 2008). Moreover, recent evidence point to CBD as a non-competitive negative allosteric modulator of CB1 and CB2 (Laprairie et al., 2015; Martínez-Pinilla et al., 2017). CBD is also an agonist of the vanilloid receptor TRPV1 (Bisogno et al., 2001), and the previous administration of a TRPV1 antagonist blocks some of CBD effects (Long et al., 2006; Hassan et al., 2014). In parallel, CBD inhibits the enzymatic hydrolysis and the uptake of the main endocannabinoid anandamide (Bisogno et al., 2001), an agonist of CB1, CB2 and TRPV1 receptors (Pertwee and Ross, 2002; Ross, 2003). The increase in anandamide levels induced by CBD seems to mediate some of its effects (Leweke et al., 2012). Moreover, in some behavioral paradigms the administration of an inhibitor of anandamide metabolism promotes effects similar to CBD (Pedrazzi et al., 2015; Stern et al., 2017).
Safety and side effects
In a subsequent study, it was observed that the administration of a Sativex-like combination attenuates all the malonate-induced alterations, namely: increased edema, decreased number of surviving cells, enhanced number of degenerating cells, strong glial activation, and increased expression of inflammatory markers (iNOS and IGF-1) (Valdeolivas et al., 2012). Although the beneficial effects of Sativex on cell survival are blocked by both CB1 or CB2 antagonists, CB2 receptors seem to have a greater role in the protective effect observed (Valdeolivas et al., 2012).