To better explain the therapeutic potential associated with the treatment of behavioral addictions, Psychedelic Stock Watch went straight to the source, addiction-treatment specialists, Awakn Life Sciences (CAN: AWKN/ US:AWKNF). Under the premise that two heads are better than one, we asked both Anthony Tennyson, CEO of Awakn and Professor Celia Morgan, Head of Ketamine Assisted Psychotherapy for Addiction with Awakn to address these questions.
We wanted them to explain to our audience:
a) The types of behavioral addictions for which psychedelic medicine may be an optimal form of treatment.
b) How treating behavioral addiction differs from (or parallels) the treatment of other mental health disorders.
c) The particular psychedelic-assisted therapies that are appropriate in treating these behavioral addictions.
With Awakn recently releasing the results of its successful Phase IIa/b clinical trial of a ketamine-assisted therapy for Alcohol Use Disorder (AUD), we also wanted to get some feedback from these principals on that significant advance.
1) Psychedelic Stock Watch is on record as identifying addiction therapy as perhaps the greatest commercial opportunity in psychedelic medicine. What motivated Awakn Life Sciences to adopt its own strong focus on addiction therapy?
AT / CM: Addiction is the biggest unmeet medical need of modern times. Substance addition (alcohol, tobacco, medicines, or illicit drugs) affected 20% of the global population while behavioral addictions (Gambling Disorder, Compulsive Sexual Behavior, Binge Eating Disorder) affected many more hundreds of millions of people globally.
For each one of these individuals there is also a partner, child, relative, friend, colleague affected.
Current treatment options are not always as effective as the could and need to be. Take AUD for an example. AUD affects 5% of the planet of 400m people. There is typically a 75% relapse rate with treatments, so 3 in 4 are back drinking within 12 months of treatment. This, in part, leads to low uptake rates for treatment, with only 16% of the those suffering from AUD seeking treatment.
This needs to improve.
And that is what we are doing and why we are doing it…we are driven tirelessly every single day to research, develop, and delivery new more effective treatemnst for addiction, to provide hope for those for whom the current treatmenst are not working.
Current treatment options are not always as effective as the could and need to be. Take AUD for an example. AUD affects 5% of the planet of 400m people. There is typically a 75% relapse rate with treatments, so 3 in 4 are back drinking within 12 months of treatment. This, in part, leads to low uptake rates for treatment, with only 16% of the those suffering from AUD seeking treatment.
This needs to improve.
And that is what we are doing and why we are doing it…we are driven tirelessly every single day to research, develop, and delivery new more effective treatemnst for addiction, to provide hope for those for whom the current treatmenst are not working.
2) How does treating addiction differ from treating other mental health disorders such as depression and anxiety?
AT / CM: Addiction is treated differently to depression and anxiety, although it is also important to emphasise these problems also co-occur very often. People with addiction often have the solution to their problems – the substance or behaviour in question – and that can make addiction very difficult to treat. Addictions may originate from a shared common vulnerability to other mental health problems, for example experiencing childhood trauma but addiction is also a learned behaviour. This learning basis of addiction, means some of the treatments are very different to other mental health disorders.
All addictions have a hallmark of having at one time been pleasurable. Experiencing something as pleasurable means you are more likely to take it again, as you learn to associate between the substance / behaviour and a good outcome. Eventually after time there is no more pleasure from the addictive behaviour but the association that has been learned is so strong that it is very difficult to shake. Some psychological therapy approaches we seek to weaken this association, to learn new healthier associations with different rewards. One such approach is contingency management that pays people small rewards to stay sober.
All addictions have a hallmark of having at one time been pleasurable. Experiencing something as pleasurable means you are more likely to take it again, as you learn to associate between the substance / behaviour and a good outcome. Eventually after time there is no more pleasure from the addictive behaviour but the association that has been learned is so strong that it is very difficult to shake. Some psychological therapy approaches we seek to weaken this association, to learn new healthier associations with different rewards. One such approach is contingency management that pays people small rewards to stay sober.
3) How does psychedelic medicine address this “reward” mechanism that reinforces both chemical and behavioral addictions?
AT / CM: Psychedelic medicine addresses the learning between rewards and outcomes. Evidence suggests that giving drugs like MDMA and ketamine after reward memories are reactivated (e.g. after someone has thinking about drinking a glass of beer) can actually weaken the memory strength, and hence the addictive behaviour. Psychedelics are also able to disrupt the networks associated with addiction, and stimulate the growth of new pathways via increased plasticity. This increased plasticity means the brain is ready to learn new healthier approaches and that psychological therapies can build on this.
4) With over 1 billion people globally grappling with addiction in the form of chemical dependencies, why has Awakn also chosen to branch into research/treatment of behavioral addictions?
AT / CM: We think it is important to tackle behavioural addictions as we have no licensed treatments for these as yet, but the number of people suffering has increased dramatically, particularly in the past few years.
5) Some of these “behavioral addictions” are well-known forms of obsessive/compulsive behavior, others are new 21st century disorders, derived from internet-related addictions. Could you please identify the behavioral addictions that Awakn is currently researching?
AT / CM: We are researching gambling, compulsive sexual behaviour, binge eating disorder and internet gaming use disorder but we are keen to explore still further indications.
6) Are there any fundamental differences in treating behavioral addictions versus chemical dependencies?
AT / CM: The two are largely treated the same, where uncovering the root cause of the addiction is important, as is tackling the maladaptive learning about the behaviour. Key differences however are that people do not need to detox from behavioural addictions before undergoing treatment, whereas with some substances this is necessary. A further difference is that with many behavioural addictions an abstinence model is not possible, for example for people with binge eating disorder (sometimes called food addiction) it is not possible to stop eating food all together. This means it is even more important to change the patient’s relationship with the addictive behaviour as they can’t simply avoid it for their whole life.
7) At what stage is Awakn Life Sciences in pursuing this research?
AT / CM: Our R&D activity is focused on new more effective therapeutics to treat addiction – that is drugs and therapy to be used in combination.
We are working with ketamine and MDMA in the near and medium term to develop the therapies side of this therapeutics package and we are working in the long term on develop our own proprietary NCEs as the drug part of that therapeutics package.
For ketamine we are focused on Alcohol Use Disorder (AUD) and Behavioral Addiction:
For ketamine we are focused on Alcohol Use Disorder (AUD) and Behavioral Addiction:
-
AUD – Awakn has in-licensed a successful Phase IIa/b trial from the University of Exeter (UoE), which was lead by Prof Celia Morgan – Awakn is working with UoE to bring this research into a Phase III trial as part of our plan to secure market authorization / regulatory approval for Ketamine-Assisted Therapy to treat AUD in UK. We would hope to have that trial initiated in late 2022. Forecast cost for this trial is only GBP2m, through costs savings achieved by UoE.
-
Behavioral Addictions – We have initiated a pre-phase I study to test a hypothesis re: Ketamine and Behavioral Addictions: Gambling Disorder, Binge Eating Disorder, Compulsive Sexual Behavior, Internet Gaming Disorder. We aim to have this activity completed in Q2 2022, and will determine next steps at that stage.
-
For MDMA we are focused on AUD, we have in-licensed that data from a successful Phase IIa trial form MDMA-Assisted Therapy for AUD. We have signed an MoU with MAPS to work together to bring this reach forward as part of a strategy to secure market authorization for MDMA-Assisted therapy to treat AUD in Europe.
-
For developing our NCEs we are at pre-clinical stage. We are developing next generation entactogens. MDMA is good for improving the effectiveness of therapy for AUD, but it takes 6 hours to work with a 6-hour recovery window. We are working to developing entactogens that work in 2 hours with a 2-hour recovery window, enable Awakn to be more effective at treating addiction in a shorter time period. Our Hit to Lead program is nearing completion with our research partner Evotec. In vitro and in vivo data shows efficacy for drug-like hits, defining chemical series for lead optimization. We would aim to start lead Optimisation initiating Q2 2022.
8) Awakn has chosen ketamine and MDMA as its drugs-of-choice in treating addiction. Let’s compare them. How/why is ketamine well-suited to the treatment of addiction?
AT / CM: Ketamine is a short-acting drug with a very well-established safety profile which makes it useful in a group of patients who often have other health problems. It disrupts the default mode network in the brain and in so doing reduces rumination. This is useful therapeutically as it disengages the individual from their normal mode of habitual thinking about addiction. The out of body experiences and the observer perspective common from ketamine can give someone new insights into their problems, particularly useful in psychological therapy.
9) What factors make MDMA a strong drug candidate for addiction therapy?
AT / CM: When MDMA is given, we also see release of the hormone oxytocin, important in bonding. This is helpful for building trust in the therapist which is important in determining how effective the therapy will be. Trust is often low in people with addiction, who may have also experienced trauma in childhood, so MDMA can be useful in building a strong therapeutic relationship. It can also be helpful for reducing self-criticism and increasing compassion, via the positive effects it induces.
Both ketamine and MDMA block reconsolidation, which is a memory process in the brain, by blocking this ketamine and MDMA both potentially have the capacity to weaken maladaptive memories. Both drugs are also psychoplastogens, increasing the plasticity of the brain following their use. This means we can weaken old maladaptive reward memories but enhance the learning of new more healthy associations, making the compounds uniquely placed to target addictions, particularly some behavioural addictions where complete abstinence is often not an option (food, sex, money).
Both ketamine and MDMA block reconsolidation, which is a memory process in the brain, by blocking this ketamine and MDMA both potentially have the capacity to weaken maladaptive memories. Both drugs are also psychoplastogens, increasing the plasticity of the brain following their use. This means we can weaken old maladaptive reward memories but enhance the learning of new more healthy associations, making the compounds uniquely placed to target addictions, particularly some behavioural addictions where complete abstinence is often not an option (food, sex, money).
10) Awakn’s research into substance abuse treatment is considerably more advanced. Please summarize the results for your recent Phase II a/b trial for a ketamine-based therapy for Alcohol Use Disorder.
AT / CM: Please see here for details of results: https://awaknlifesciences.com/phase-ii-a-b-results.
Over 4-week period, we gave three infusions of ketamine with 7 sessions of psychotherapy.
Six months after the start of treatment months our study showed abstinence levels / zero drinking at 86% - compared to 2 % before starting. The best results were seen in the ketamine and therapy group.
Over 4-week period, we gave three infusions of ketamine with 7 sessions of psychotherapy.
Six months after the start of treatment months our study showed abstinence levels / zero drinking at 86% - compared to 2 % before starting. The best results were seen in the ketamine and therapy group.
11) How do these results compare with conventional therapies for Alcohol Use Disorder?
AT / CM: Favorably, as we noted above, there is typically a 75% relapse rate at 12 months following treatment.
12) How far do you see psychedelic medicine for the treatment of addiction evolving over the next 5 years?
AT: I think the new approaches we are seeing to treating addiction here may continue to evolve and be refined as we see new chemical entities entering the market. Using such medicines to weaken maladaptive memories by disrupting reconsolidation and enhance new more adaptive learning, through the psychoplastogen properties of these drugs, has a real potential to make a step change in addiction treatment worldwide.