For the moment, no firm conclusions can be drawn about the safety and efficacy of cannabinoid-based drugs hemp oil for pain in older individuals, which represent the population most likely to be affected by ADReference 557. Results from in silico and in vitro experiments suggest Δ9-THC could bind to and competitively inhibit acetylcholinesterase, which in the context of AD functions as a molecular chaperone and accelerates the formation of amyloid fibrils and forms stable complexes with AβReference 1154. In this way, Δ9-THC blocked the amyloidogenic effect of acetylcholinesterase, diminishing Aβ aggregationReference 1154. Other in vitro studies suggest that CBD may have neuroprotective, anti-oxidant, and anti-apoptotic effects, as well as the ability to prevent tau protein hyperphosphorylation in cellular models of ADReference 1155-Reference 1157.
A subsequent double-blind, randomized, placebo-controlled, parallel-group clinical study investigated the effects of dronabinol on colonic sensory and motor functions of healthy human volunteersReference 1198. Administration of a 7.5 mg dose of dronabinol significantly increased colonic compliance, especially in females, and reduced pre- and post-prandial phasic colonic motility and pressure.
It has also been shown that endocannabinoids can prevent Aβ-induced lysosomal permeabilization and subsequent neuronal apoptosis in vitroReference 1153. Additionally, the therapeutic potential of CBD in the treatment of schizophrenia/psychosis, while promising, requires further research. A pseudo-randomized, placebo-controlled, double-blind, within-subject clinical study showed that pre-treatment of healthy human subjects with CBD (5 mg i.v.), but not placebo, diminished the emergence of positive psychotic symptoms 30 min after i.v.
There have been very few clinical studies of cannabis or cannabinoids for the treatment of AD. A 2009 Cochrane database systematic review of cannabinoids for the treatment of dementia concluded that there was insufficient clinical evidence to suggest that cannabinoids can be effective at improving disturbed behavior in dementia or in the treatment of other symptoms of dementiaReference 1162.
Colonic compliance is defined as the change in distensibility of the colon in response to a change in applied intracolonic pressure and it is used as a measure of colonic viscoelastic properties and as an indicator of colonic motor/contractile activityReference 1198-Reference 1200. Decreased compliance is typically associated with urgency and diarrhea, while increased compliance is typically associated with constipationReference 1199Reference 1201. An increase in colonic compliance in this setting could indicate a return towards proper colonic function. In contrast to the results seen in the pre-clinical rodent studies, dronabinol increased the sensory rating of pain but did not affect the sensory rating of gas, or the thresholds for first sensation of either gas or pain during experimentally-induced random phasic distensionsReference 1198.