Cannabis entourage compounds as an antidote to unwanted side effects  

 

Cannabis is known to produce a wide variety of effects from rendering an individual wide-awake to sending them into a sound sleep. While most patients can benefit from the medicinal effects of THC, some patients may suffer from bouts of anxiety while medicating.

 

Acute overdose incidents involving THC or THC-predominant cannabis strains usually consist of self-limited panic reactions.  Intervention is generally not necessary, and supportive counselling (reassurance or ‘talking down’) is sufficient without any complications or after effects.

 

Ethanol does not reduce cannabis intoxication. (Mello and Mendelson, 1978).

 

The historical suggestions below for cannabis antidotes are supported by modern scientific rationales for the claims, and provide additional evidence of synergy. (Berenbaum, 1989; Wagner and Ulrich-Merzenich, 2009).

 

Cannabidiol (CBD)

 

CBD is an essential component to combat the unwelcome effects of using THC rich cannabis, such as anxiety.  CBD modulates the psychoactivity of THC and reduces its adverse event profile. (Russo and Guy, 2006).  

 

Terpenes

 

Another option to combat the unwelcome side effects may be to introduce terpenes from other plant sources to mitigate the effects. Scientists have explored how these aromatic oils synergize and mitigate the active cannabinoids contributing to an entourage effect.  In the article “Taming THC,” scientists report the discovery of more than a hundred terpenes that “may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts.”

 

Lemon

 

Lemon juice, which normally contains small terpenoid titres, has been used as an anitdote over the ages to mitigate unwanted side effects of cannabis. In 10th century Persia, Al-Razi offered a prescription in his Manafi al-agdhiya wa-daf madarri-ha (p. 248),  "to avoid these harms (from ingestion of cannabis seeds or hashish), one should drink fresh water and ice or eat any acid fruits." (Lozano, 1993, p. 124) This concept was repeated by various authorities through the ages, including ibn Sina (ibn Sina (Avicenna), 1294), and Ibn al-Baytar (ibn al-Baytar, 1291).

 

In 1948 Robert Christison subsequently cited lemon as an antidote to acute intoxication in numerous cases. Christison wrote about the morning-after residual and lemonade: "Next morning there was an ordinary appetite, much torpidity, great defect and shortness of memory, extreme apparent protraction of time, but no peculiarity of articulation or other effect; and these symptoms lasted until 2 P.M., when they ceased entirely in a few minutes after taking lemonade." (Christison, 1848) (p. 973)

 

In the 19th century, the sentiment was repeated by Bayard Taylor after his travels in Syria (Taylor, 1855), and Fitzhugh Ludlow after his voluntary experiments with ever higher cannabis extract doses in the USA (Ludlow, 1857),  by Calkins (1871), who noted that the suggestion of a friend in Tunis that lemon retained the confidence of cure of overdoses by cannabis users in that region.

 

Lemon juice, is traditionally used in North Africa by the inclusion in drinks of the limonene-rich rind, as evidenced by the recipe for Agua Limón from modern Morocco (Morse and Mamane, 2001).

 

In his comprehensive review of cannabis in the first half of the 20th century, Walton once more supported lemon as prescription for overdose. (Walton, 1938).

 

Pine  

 

The cannabis terpenoid, α-pinene, has been characterised as a potent inhibitor of THC (Miyazawa and Yamafuji, 2005), supporting the hypothesis of another antidote to THC contained in cannabis itself.  Historical precedents also support pinene in this pharmacological role. 

 

In the first century, Pliny wrote of cannabis in his Natural History, Book XXIV (Pliny, 1980, p. 164): The gelotophyllis [‘leaves of laughter’ = cannabis] grows in Bactria and along the Borysthenes. If this be taken in myrrh and wine all kinds of phantoms beset the mind, causing laughter which persists until the kernels of pine-nuts are taken with pepper and honey in palm wine. (Salvadeo et al., 2007).

 

Pistachio nuts

 

The ripe fruits of Pistacia terebinthus similarly contain pinene (Couladis et al., 2003). In the 13th century, (-Ukbari also suggested pistachio nuts as a cannabis antidote (Lozano, 1993).

 

Black pepper

 

The black pepper might offer the mental clarity afforded by pinene, sedation via myrcene and helpful contributions by β-caryophyllene. A few sniffs of the black pepper has been reported by patients to have an almost immediate effect. Chewing on pepper corns may take up to an hour to take effect, but that may be too long a delay for some patients. 

 

Calamus root

 

Calamus root has been used as a traditional antidote from the Ayurvedic tradition of India (Lad, 1990, p. 131): "Calamus root is the best antidote for the ill effects of marijuana. . . . if one smokes a pinch of calamus root powder with the marijuana, this herb will completely neutralize the toxic side effects of the drug."

 

This claim has gained credence through anecdotal accounts on the Internet, and from scientific case reports and analysis that have reported "clearer thinking and improved memory with the cannabis calamus combination," 

(McPartland et al., 2008); and "calamus contains beta-asarone, an acetylcholinesterase inhibitor with 10% of the potency of physotigmine" (Mukherjee et al., 2007).