Mechoulam and co-workers (1976) have summarized the 
current status of our knowledge of structure-activity relation- 
ships in the cannabinoid area. With regard to psychotomimetic 
activity, the structural requirements may be summarized as 
follows: 
1. A benzopyran (or xanthene) type of structure with a 
hydroxyl group at the | aromatic position and an alkyl group on 
the 3 aromatic position seem to be required. Opening of the 
pyran ring leads to complete loss of activity. 
2. The aromatic hydroxyl group has to be free or esterified. 
Blocking of the hydroxyl group as an ether inactivates the 
molecule. 
3. When alkyl groups are substituted on the phenolic ring 
at C-3, activity is retained. Substitution at C-5 eliminates 
activity. Electronegative groups such as carboxyl, carbometh- 
oxyl and acetyl at either C-3 or C-5 eliminate activity. 
4. A certain length of the aromatic side chain at C-3 is a 
requirement for activity. Branching of the side chain may lead to 
substantial increase in potency. A 1,2-dimethylheptyl or a 1,1- 
dimethylheptyl side chain seems to be best. 
5. Not all of the theoretically possible THC’s are active. Thus, 
A* and A’-THC are active in the 3R,4R series only; A’-THC and 
A''-THC are inactive; A'*-THC is active: A’-3,4-cis-THC is in- 
active. 
6. The terpenoid and pyran rings may be considerably modi- 
fied. These modifications do not seem to follow a regular 
pattern, and even tentative rules cannot yet be put forward. 
€. NEW POTENTIAL HAZARD OF MARIHUANA USE. Recent attempts 
to increase the “potency” of marihuana by spraying whole 
growing plants with liquid fertilizer have been reported. It has 
been pointed out that this practice could be dangerous on the 
theoretical grounds that such treatment might cause the forma- 
tion of carcinogenic N-nitrosamines (Farnsworth and Cordell 
1976). Fertilizers containing nitrate can potentially initiate N- 
nitroso derivitization of secondary amines known to be present 
in marihuana, with the reaction being accelerated by the pres- 
ence of any compounds with o-hydroxy phenolic (catechol) 
groups. It has recently been shown that marihuana does contain 
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