This blog is part of a series of articles looking at how chemical, pharmaceutical and research organisations can easily stay compliant against controlled drug and related regulations globally. We also have blog posts on research exemptions and how to asses if you are likely to have controlled and regulated substances in your research collections.
A common misconception when trying to identify if a chemical is controlled under the US Controlled Substances Act is to assume that you can simply download a list of controlled substances and compare.
Indeed google reports that in 2022 on average search terms such as ‘dea list of controlled substances’, ‘controlled substance list’ or ‘list of controlled drugs’ are used 4000 times per month, so you are not alone in assuming this
In this blog I’ll explain why trying to compare to a list of substance names is highly error prone and likely to lead to compliance issues and more importantly what you can do to avoid these pitfalls.
It seems like it should be easy right? Get a let a of controlled drugs, compare it your chemicals to see if any are controlled. So why isn’t it that easy?
Many ways to name a molecule
Firstly, the name given in the schedules is a typical name. However chemicals can be known by hundreds of names and identifiers. If the name you have does to 100% match the name in the schedule you will miss it.
For example 5-MeO-DIPT (CAS 4021-34-5) is a schedule 1 controlled substance in the USA. However in the Controlled Substances Act its listed as 5-Methoxy-N,N-diisopropyltryptamine, while it is also known as 3-[2-(Diisopropylamino)ethyl]-5-methoxyindol; N-Isopropyl-N-[(5methoxy-1H-indol-3-yl)ethyl]propan-2-amin; 5-Methoxy-N,N-diisopropyltryptamine; 5-Methoxy-N,N-diisopropyltryptamine by other regulators outside the USA. Pubchem lists over 30 different synonyms or chemical names for the same molecule.
When you consider that there are hundreds of named substances in controlled drug laws, each with dozens of potential common names you can quickly see why keyword or name searching won’t work.
Also, what happens if you don't have the name - just a chemical structure, a name search won't help with this
Variations of the named chemical
Most of the time, the named molecule is just the example. Its very common for all known ethers, esters, salts, positional and stereoisomers to also be controlled. You won’t find the names / numbers of these variations listed, you have work it out yourself.
Analogues are also controlled
Often as well as defined variations, analogues of a controlled substance are also considered controlled. This is very common in the USA, Mexico and Canada, but less so European countries or China who prefer to use defined chemical space / chemical families instead. What is defined as an analogues is subjective and ultimately upto the courts to decide. However you can computationally try and predict if a chemical will be considered an analogue (read our guide to this here) and take a risk based decision on whether you wish to treat it as controlled or not.
Controlled chemical families
In an effort to avoid “legal highs” where a small chemical change is made to a molecule to technically take it out of control, but retain its narcotic effect, legislators often choose to control entire chemical families of similar molecules. These are often known as 'generic statements', 'Markush rules', or 'chemical family' based controls. Whereas “analogues” is unclear in what is meant, these statement are very precise (although complicated) in defining exactly what chemicals are controlled or not, so easy to prosecute.
Within the USA, ‘Fentanyl like chemicals’ and ‘synthetic cannabinoids’ are covered by these generic statements. An example of which is below (the full wording is available here)
‘…compounds structurally related to fentanyl by one or more of the following modifications: A) Replacement of the phenyl portion of the phenylethyl group by any monocycle, whether or not further substituted in or on the monocycle. B) Substitution in or on the phenylethyl group with alkyl, alkenyl, alkoxyl, hydroxyl, halo, haloalkyl, amino or nitro groups. C) Substitution in or on the piperidine ring with alkyl, alkenyl..........’
This is clearly very complicated to understand and cannot be searched for via name matching. We've written seperate blog posts on generic statements if you wish to read more
If you cannot rely on name matching, how do you easily check the controlled drug lists?
So if name searching / list matching does not work, what can you do to easily check if a chemical is regulated.
The good news is that all these issues can be addressed if you encode the rules and substances in the legislation structurally and then search them by chemical structure. In doing this you can enter a chemical name or a structure and instantly know if it’s a controlled drug or not by comparing its chemical structure. Fortunately the chemical search wizards and controlled drug legislation experts at Scitegrity have already done this for you with Controlled Substances Squared. Simple enter your chemical(s) names or structures, hit check and instantly know whether its on the the Controlled Substances Act lists of controlled drugs, analogues, chemical space and more.
However, please note the warnings on these official pages such as…
“This document is a general reference and not a comprehensive list. This list describes the basic or parent chemical and does not describe the salts, isomers and salts of isomers, esters, ethers and derivatives which may also be controlled substances.” - DEA