In a pre-review report by W.H.O we can found some evidence that CBD can be converted to tetrahydrocannabinol (THC), a Schedule 1 substance under the United Nations Convention on Psychotropic Substances 1971.
Two main methods have been reported and there has been some investigation into whether this occurs spontaneously in vivo.
Conversion in the laboratory
Under experimental conditions, it has been demonstrated that heating CBD in solutions of some acids catalyses cyclizations within the CBD molecule resulting in delta-9-THC.
Gaoni and Mechoulam have published several papers regarding methods of converting CBD to other cannabinoids including THC, however the yields vary and purity is unclear.
A version of this method has been reported on a drug user forum. It suggests dissolving CBD in sulphuric acid/acetic acid and leaving it for anywhere from 3 hours to 3 days to obtain delta-9-THC and delta-8-THC. After 3 hours, the author states that CBD has been converted into 52% delta-9-THC and 2% delta-8-THC.
A patent (US 2004/0143126 A1) on the conversion of CBD to delta-9-THC details a method involving the addition of BF3Et2O (50 µl), under nitrogen atmosphere, to an ice cold solution of CBD (300 mg) in dry methylene chloride (15 ml). The solution is stirred at 0° C for 1 hour, followed by the addition of saturated aqueous solution of NaHCO3 (2 ml) until the red colour fades. The organic layer is removed, washed with water, dried over MgSO4 and evaporated. The composition of the oil obtained (determined by HPLC) is: trans-delta8-isoTHC 27%, delta-9-THC 66.7%. The oil is then chromatographed on silica gel column (20 g) and eluted with petroleum ether followed by graded mixtures, up to 2:98
of ether in petroleum ether. The first fractioneluted was the delta8-isoTHC (30 mg, 9.5%) followed by a mixture of delta8-iso THC and delta-9-THC (100 mg). The last compound to be eluted was the delta-9-THC (172 mg, 57%). The purity of delta-9-THC (as determined by HPLC) is 98.7%. [29]
Spontaneous conversion
It has been proposed that the conversion of CBD to delta-9-THC in the presence of
acid could occur in the human gut. Such conversion could be of importance if CBD is
administered orally.
Two in vitro studies have used simulated gastric fluid to demonstrate the potential for this conversion.
The first reported the formation of analytically confirmed delta-9-THC and delta-8-THC when CBD was exposed to simulated gastric fluid without enzymes at 37ºC. The authors concluded that that the acidic environment during normal gastrointestinal transit could expose orally CBD- treated patients to levels of THC and other psychoactive cannabinoids that mayexceed the threshold for a physiological response.
The second in vitro study also reported the formation of delta-9-THC along with other cannabinoid products in artificial gastric juice without pepsin. The conversion rate of CBD to THC was only2.9%.
The predictive value of these in vitro studies for humans administering cannabidiol
orally has been questioned as simulated gastric fluid does not exactly replicate
physiological conditions in the stomach.
Furthermore, spontaneous conversion of CBD to delta-9-THC has not been demonstrated in humans undergoing CBD treatment. For example, in a six week clinical study in Huntington’s disease patients who were administered CBD 700 mg/day, the CBD average plasma concentration range was 5.9-11.2 ng/mL with no delta-9-THC detected.
In humans, THC effects are characterised by impairment of psychomotor and
cognitive performance, and a range of physical effects including increased heart rate
and dry mouth. In general, clinical studies have reported that even high doses of oral
CBD do not cause the those effects that are characteristic for THC and for cannabis
rich in THC.
For example, in a study of healthy volunteers administered 200mg oral CBD, CBD did not produce any impairments of motor or psychomotor performance.
A number of other studies involving high doses of CBD were recently summarized by Grotenhermen they concluded that high doses of oral CBD consistently fail to demonstrate significant effects or demonstrate effects opposite to those of THC.
While it has been suggested that further large-scale human studies are needed to
explore the gastric conversion and potential THC-like side effects following oral CBD
administration [36], it is very unlikely that oral cannabidiol will be shown to result in
THC concentrations sufficient to induce any meaningful effects.
Source: https://www.who.int/medicines
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