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Cannabis Antedotes ?

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ran across this article about historical antedotes to cannabis intoxication / side effects.

not sure if useful but here you go for funs.




Taming THC: cannabis entourage compounds as antidotes to intoxication

Various sources highlight the limited therapeutic index of pure THC, when given intravenously (D'Souza et al., 2004) or orally (Favrat et al., 2005), especially in people previously naïve to its effects. Acute overdose incidents involving THC or THC-predominant cannabis usually consist of self-limited panic reactions or toxic psychoses, for which no pharmacological intervention is generally necessary, and supportive counselling (reassurance or ‘talking down’) is sufficient to allow resolution without sequelae. CBD modulates the psychoactivity of THC and reduces its adverse event profile (Russo and Guy, 2006), highlighted by recent results above described. Could it be, however, that other cannabis components offer additional attenuation of the less undesirable effects of THC? History provides some clues.

In 10th century Persia, Al-Razi offered a prescription in his Manafi al-agdhiya wa-daf madarri-ha (p. 248), rendered (Lozano, 1993, p. 124; translation EBR) ‘– and to avoid these harms {from ingestion of cannabis seeds or hashish}, one should drink fresh water and ice or eat any acid fruits’. This concept was repeated in various forms by various authorities through the ages, including ibn Sina (ibn Sina (Avicenna), 1294), and Ibn al-Baytar (ibn al-Baytar, 1291), until O'Shaughnessy brought Indian hemp to Britain in 1843 (O'Shaughnessy, 1843). Robert Christison subsequently cited lemon (Figure 3A) as an antidote to acute intoxication 
in numerous cases (Christison, 1851) and this excerpt regarding morning-after residua (Christison, 1848) (p. 973):
Figure 3
Ancient cannabis antidotes. (A) Lemon (Citrus limon). (B) Calamus plant roots (Acorus calamus). (C) Pine nuts (Pinus spp.). (D) Black pepper (Piper nigrum).

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.

Literary icons on both sides of the Atlantic espoused similar support for the citrus cure in the 19th century, notably Bayard Taylor after travels in Syria (Taylor, 1855), and Fitzhugh Ludlow after his voluntary experiments with ever higher cannabis extract doses in the USA (Ludlow, 1857). The sentiment was repeated by Calkins (1871), who noted the suggestion of a friend in Tunis that lemon retained the confidence of cure of overdoses by cannabis users in that region. This is supported by the observation that lemon juice, which normally contains small terpenoid titres, is traditionally enhanced 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 its prescription (Walton, 1938).

Another traditional antidote to cannabis employing Acorus calamus (Figure 3B) is evident 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, not only through force of anecdotal accounts that abound on the Internet, but with formal scientific case reports and scientific analysis (McPartland et al., 2008) documenting clearer thinking and improved memory with the cannabis–calamus combination, and with provision of a scientific rationale: calamus contains beta-asarone, an acetylcholinesterase inhibitor with 10% of the potency of physotigmine (Mukherjee et al., 2007). Interestingly, the cannabis terpenoid, a-pinene, also has been characterized as a potent inhibitor of that enzyme (Miyazawa and Yamafuji, 2005), bolstering the hypothesis of a second antidote to THC contained in cannabis itself. Historical precedents also support pinene in this pharmacological role.

In the firstt 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.

Of the components, palm wine is perhaps the most mysterious. Ethanol does not reduce cannabis intoxication (Mello and Mendelson, 1978). However, ancient wines were stored in clay pots or goatskins, and required preservation, usually with addition of pine tar or terebinth resin (from Pistacia spp.; McGovern et al., 2009). Pine tar is rich in pinene, as is terebinth resin (from Pistacia terebinthus; Tsokou et al., 2007), while the latter also contains limonene (Duru et al., 2003). Likewise, the pine nuts (Figure 3C) prescribed by Pliny the Elder harbour pinene, along 
with additional limonene (Salvadeo et al., 2007). Al-Ukbari also suggested pistachio nuts as a cannabis antidote in the 13th century (Lozano, 1993), and the ripe fruits of Pistacia terebinthus similarly contain pinene (Couladis et al., 2003). The black pepper (Figure 3D), 
might offer the mental clarity afforded by pinene, sedation via myrcene and helpful contributions by ß-caryophyllene. The historical suggestions for cannabis antidotes are thus supported by modern scientific rationales for the claims, and if proven experimentally would provide additional evidence of synergy (Berenbaum, 1989; Wagner and Ulrich-Merzenich, 2009).

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