On the 17th of June 2014, The American Society of Anaesthesiologists released a statement in which a team lead by Irving Wainer, PhD, claimed to have discovered a compound “that may treat symptoms of depression just as effectively and rapidly as ketamine, without the unwanted side effects associated with the psychoactive drug”. This major breakthrough could lead to a revolution in the treatment of mental illnesses and neurodegenerative diseases.

Ketamine is one of the most widely used and controversial medical drugs in existence. The hallucinatory, dissociative trance produced by the substance has led it to become a common recreational drug (known popularly as “ket” or “k”), and it was reclassified from Class C to Class B in December 2013, in concordance with its rise in popularity.

Ever since it was first synthesised in 1962, ketamine has been used medically to induce states of general anaesthesia, particularly in cases of opiate allergies. It is also a common ingredient in tranquillising “cocktails” used to sedate animals such as rodents, dogs and horses in order to induce a state of general anaesthesia or, in the cases of the larger animals, manage the levels of pain caused by the operation.

Ketamine induces a cataleptic state; this is a state in which muscle rigidity is common, and a reduction in sensitivity to pain accompanied by an unnatural steadiness of posture indicate a lack of engagement with external stimuli. It also has, more recently, been discovered to have a strong effect on the glutamate neurotransmitter system, which has become a focus in recent studies on the treatment of depression. In human studies it has been shown to have a rapid and drastic positive effect on the mood of the subject, with 64 percent of patients responding significantly positively to the drug in a 2013 study, compared with a 28 percent response to the current leading product on the market (see further reading).

Unfortunately, despite this array of positive effects, up to 12 percent of ketamine users, recreational or medical, are reported to experience severe side-effects, including but not limited to respiratory, nervous and cardiovascular malfunctions. Even under comprehensive medical control, ketamine is still a highly dangerous drug. In drastic cases such as the need for general anaesthesia, the benefit outweighs the risk, but in cases such as depression the scope for the use of ketamine “is limited because the drug is administered intravenously and may produce adverse effects such as hallucinations and sedation to the point of anesthesia”, said Dr Wainer. Fortunately, thanks to his team, the search for a safe alternative has taken a huge step towards reality in the past week.

This breakthrough compound, which is called hydroxynorketamine (known as HNK), has been known to exist for several years, as it is one of the products of ketamine breakdown in the human body. In this study, the team chose to investigate if this broken down form of the drug retained its medical viability. This methodology is common in the field of pharmacology, as the human body often breaks down compounds to less harmful constituents, very occasionally retaining their original effects.

HNK has now been successfully tested on rats, showing a similar set of effects to ketamine, displaying “potent and rapid anti-depressant effects”. The team was also pleasantly surprised to discover that HNK had more to offer, stimulating the regeneration of neurone pathways (a possible breakthrough in the treatment of neurodegenerative disease) and reducing the production of D-serine, a chemical which, when overproduced, has been proven to be a sign of neurodegenerative disorders.

Dr Wainer, who is also currently the coauthor of a pending patent on the use of ketamine as a treatment for bipolar disorder and depression, has suggested that HNK could be the most efficient anti-depressant on the market, with countless applications including the treatment of Alzheimer’s and Parkinson’s disease. Unlike ketamine, which must be administered through injections, HNK should be available in oral form. Dr Wainer said that he forsees a future where HNK is utilised as a “daily, self-administered treatment”, and has called it a “very exciting… potentially therapeutic and important compound”.

 

Further reading:

http://www.asahq.org/Home/For%20the%20Public%20and%20Media/Press%20Room/Anesthesiology%20and%20Other%20Scientific%20Press%20Releases/July%20Ketamine.aspx

http://ajp.psychiatryonline.org/article.aspx?articleID=1733362