Page 8 - CANNABIDIOL (CBD) Critical Review Report Geneva, 4-7 June 2018 World Health Organization

B. Chemical Structure

Molecular Formula: C21H30O2
Molecular Weight: 314.469 g/mol

C. Stereoisomers

Cannabidiol (CBD) is normally taken to refer to the naturally occurring (-)-
enantiomer. (+) CBD has been synthesized [4] but has received little attention.

(+) CBD has been shown to have modest affinity at CB1 and CB2 receptors
unlike (-) CBD ((+)-CBD Ki= 0.84 µM at CB1), whereas both compounds
inhibited anandamide hydrolysis and were agonists at the vanilloid type 1
(VR1) receptor at which capsaicin acts. [5] The (+)-CBD isomer was more
active than the (-)-CBD-isomer as an anticonvulsant agent in a mouse seizure
model. [6] However, to date, there is no substantive evidence as to whether
(+)-CBD is likely to cause THC-like psychoactive effects.

D. Methods and Ease of Illicit Manufacturing

Synthesis of CBD in vitro:
Synthetic routes are available for the production of CBD, but some of the
published methods yield only small amounts of CBD. The two most efficient
routes are:

1) The condensation of (+)-e-mentha-diene-l-01 with olivetol in the presence
of weak acids (oxalic, picric or maleic acid). The isomer obtained in this
reaction may be converted to CBD with BF3-etherate by a retro-Friedel-
Crafts reaction, followed by recombination. However, with this reagent the
reaction proceeds further causing cyclisation of CBD to delta-1-THC and
iso-THC [7]

2) A one step reaction for CBD synthesis utilizes boron trifluoride (BF3)-
etherate on alumina as condensing reagent in the reaction of (+)-e-mentha-
diene-l-01 with olivetol on a 0.8mmol scale (refer to Figure 1). This results
in CBD as the major product, with 55% yield as chromatographically pure

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