Dimethylheptylpyran

Dimethylheptylpyran (DMHP, 3-(1,2- longer than 48 hours.

dimethylheptyl)-Δ6a,10a -THC, 1,2-dimethylheptyl- Cannabinoids as a class are generally safe compounds
Δ3 THC, A-40824, EA-1476) is a synthetic analogue of
with a large safety margin, making potent cannabi-
THC, which was invented in 1949 during attempts to noid drugs ideal as potential non-lethal incapacitating
elucidate the structure of Δ9 -THC, the active component
agents. DMHP and its esters produce sedation and
of cannabis.[1] DMHP is a pale yellow, viscous oil which mild hallucinogenic effects similar to large doses of
is insoluble in water, but dissolves in alcohol or non-polar THC, but in addition to this they also cause pronounced
solvents. hypotension (low blood pressure) which occurs at doses
well below the hallucinogenic dose, and can lead to severe
dizziness, fainting, ataxia and muscle weakness, sufficient
1 Effects to make it difficult to stand upright or carry out any kind
of vigorous physical activity (an effect known colloqui-
DMHP is similar in structure to THC, differing only in ally as “couch lock”). The acute toxicity of DMHP was
the position of one double bond, and the replacement of found to be low in both human and animal studies, with
the 3-pentyl chain with a 3-(1,2-dimethylheptyl) chain.[2] the ratio of ED50 to LD50 (Therapeutic Index) in animals
It produces similar activity to THC, such as sedative ef- being around 2000x, with death ultimately resulting from
fects, but is considerably more potent,[3] especially having a combination of hypotension and hypothermia and pre-
much stronger analgesic and anticonvulsant effects than ventable with supportive treatment.
THC, although comparatively weaker psychological ef- The combination of strong incapacitating effects and a
fects. It is thought to act as a CB1 agonist, in a similar favourable safety margin led the Edgewood Arsenal team
manner to other cannabinoid derivatives.[4] to conclude that DMHP and its derivatives, especially
the O-acetyl ester of the most active isomer, EA-2233-2,
were among the more promising non-lethal incapacitating
2 Investigation as non-lethal inca- agents to come out of their research program. However
they were disadvantaged by producing severe hypoten-
pacitating agent sion at incapacitating doses, and were not as effective as
the more widely publicised anticholinergic agents such
DMHP and its O-acetate ester were extensively inves- as 3-Quinuclidinyl benzilate which had also already been
tigated by the US military chemical weapons program weaponised.[6] Funding for continued development was
in the Edgewood Arsenal experiments, as possible non- ultimately not approved, and the cannabinoid research
lethal incapacitating agents.[5] program was indefinitely suspended along with the rest
DMHP has three stereocenters and consequently has of the Edgewood Arsenal experiments in the late 1970s,
eight possible stereoisomers, which differ considerably in accordance with the US commitment to cease research
in potency. The racemic mix of all eight isomers of into chemical weapons under disarmament treaties.
the O-acetyl ester was given the code number EA-2233,
with the eight individual isomers numbered EA-2233-1
through EA-2233-8. The most potent isomer was EA- 3 Isomerism
2233-2, with an active dose range in humans of 0.5–2.8
μg/kg (i.e. ~35–200 μg for a 70 kg adult). Active doses
Note that 6H-dibenzo[b,d]pyran-1-ol is the same as 6H-
varied markedly between individuals, but when the dose
benzo[c]chromen-1-ol.
of EA-2233 was taken up to 1–2 mg, all volunteers were
considered to be incapable of performing military duties, See also: Tetrahydrocannabinol § Isomerism
with the effects lasting as long as 2–3 days.
DMHP is metabolised in a similar manner to THC, pro-
ducing the active metabolite 11-hydroxy-DMHP, but the
lipophilicity of DMHP is even higher than that of THC 4 References
itself, giving it a long duration of action and an ex-
tended half-life in the body of between 20–39 hours, with [1] Adams R, Harfenist M, Loewe S (1949). Jour-
the half-life of the 11-hydroxy-DMHP metabolite being nal of the American Chemical Society 71 (5): 1624.

1
2 4 REFERENCES

Dibenzopyran and monoterpenoid numbering of tetrahydro-

cannabinol derivatives

doi:10.1021/ja01173a023. Missing or empty |title=

(help)

[2] Razdan RK (1980). “The Total Synthesis

of Cannabinoids”. Total Synthesis of Natural
Products, Volume 4 (PDF). Wiley-Interscience.
doi:10.1002/9780470129678.ch2. ISBN
9780471054603.

[3] Wilkison, DM; Pontzer, N; Hosko, MJ (1982). “Slow-

ing of cortical somatosensory evoked activity by delta 9-
tetrahydrocannabinol and dimethylheptylpyran in alpha-
chloralose-anesthetized cats”. Neuropharmacology 21
(7): 705–9. doi:10.1016/0028-3908(82)90014-4. PMID
6289158.

[4] Parker, LA; Mechoulam, R (2003). “Cannabinoid ag-

onists and antagonists modulate lithium-induced condi-
tioned gaping in rats”. Integrative physiological and be-
havioral science : the official journal of the Pavlovian So-
ciety 38 (2): 133–45. doi:10.1007/BF02688831. PMID
14527182.

[5] Possible Long-Term Health Effects of Short-Term Expo-

sure To Chemical Agents. Vol. 2: Cholinesterase Re-
activators, Psychochemicals and Irritants and Vesicants.
Commission on Life Sciences. The National Academies
Press. 1984. pp. 79–99.

[6] Ketchum, James S. (2006) Chemical Warfare Secrets Al-

most Forgotten. ChemBooks Inc. ISBN 978-1-4243-
0080-8
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