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Alchemica

Instilling 'motivation to quit' through serotonergic plant medicines and things like CBD as relapse prevention

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Anyone use CBD in the context of relapse prevention? Keen to hear any experiences with such. I've had good break aways from things like alcohol but relapse prevention is an under-addressed area in medicine. CBD is often good but limited by cost-prohibitiveness at the doses required for some.

 

Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle

 

Full text: http://sci-hub.tw/https://www.nature.com/articles/s41386-018-0050-8

 

The use of serotonergics in mood disorders is well established and their use in SUDs is gaining traction. Things like psilocybin can facilitate abstinence and behavioural change, what is there for relapse prevention?

 

As an example for motivating substance abuse cessation: "A recent pilot study in alcohol-dependent patients on the efficacy of psilocybin in alcohol dependence showed a significant reduction in both percentage of drinking days and heavy drinking days, with large effect sizes. Furthermore, a recent study investigating psilocybin in tobacco dependence demonstrated that 80% of the participants had quit smoking after a 6-month follow-up, thereby substantially exceeding success rates for other behavioral and/or pharmacological therapies. In the latter study, participants were also asked why they thought psilocybin helped in quitting smoking. The most common reasons were ‘changing orientation toward the future, so that long-term benefits outweighed immediate desires (73%); strengthening participants’ beliefs in their ability to quit (73%); and changing life priorities/values, such that smoking was no longer more important than quitting (68%)’" [1]

 

Successful serotonergic interventions activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions.

 

CBD has potential rapid acting antidepressant activity potentially mediated by 5-HT1ARS. CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.

 

Things like CBD are finding potential use as "relapse prevention aids": CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. This may be mediated by 5-HT1ARs. 5-HT1A receptors as a target through which CBD produced its proneurogenic/mood, anti-anxiety actions and amelioration of stress-induced reinstatement.

 

While I believe the acute mood improvements and behavioural change often comes via 5-HT2ARs inducing 'new ways of thinking, motivating behavioural shifts and providing spiritual insight', maintaining efficacy is another intriguing question. New treatments for both treatment resistant depression and SUDs are urgently needed. 5-HT-mediated changes in emotion and stress regulation (HPA axis etc) can strongly affect both mood and addiction-related disturbances which often feed each other

 

Problem is, while they're often effective, it's often not a great idea to keep throwing more 5-HT2A selective substances at your brain to ease pathology. Can you get at issues and restore emotional balance through 5-HT1ARs? DRN 5-HT1A receptor availability is linked specifically to the processing of aversive emotions in the amygdala and the modulation of amygdala-cortical connectivity.

 

How much therapeutic potential comes from 5-HT2A vs 5-HT1A? 5-HT1A receptor agonists are effective against emotional changes produced by stressful stimuli - activation of the adrenocortical system via 5-HT1A receptors may facilitate some adaptive mechanism(s) involved in the recognition of and/or ability to cope with stressful situations

 

While 5-HT2A receptor-mediated signaling is implicated in emotional processes, the neuroendocrine system, and behavioural flexibility what happens due to other serotonergic receptor actions? 5-HT1A receptors are believed to be crucial in physiological processes linked to emotional balance

 

Altered 5-HT1AR expression is observed in emotional and behavioural disorders. Studies in Schizophrenia reported increases in 5-HT1AR density in the prefrontal cortex in the approximate range of 15–80% Recent studies in Alzheimer’s disease have shown that reduced 5-HT1AR binding in the temporal cortex correlates with aggressive behavior in Alzheimer’s disease

 

It is proposed that the nonselective interaction of psychedelics with other 5-HT receptors contributes to behavioural effects, over being solely mediated by 5-HT2A

 

Some investigators propose that postsynaptic 5-HT1A and 5-HT2A receptors have functionally opposing effects, that a disturbed balance of these receptors may be contributing to the pathophysiology of depression, anxiety, and impulsivity, and that restoring this balance is necessary for therapeutic action. 5-HT1A receptor agonism may act to buffer 5-HT2A-mediated psychedelic effects.

 

While 5-HT2A receptors may strongly influence the emotional state of an individual, several researchers to propose that postsynaptic 5-HT1A and 5-HT2A receptors exert opposing effects in the regulation of mood. A disturbed balance between these receptors has been thought to contribute to depression but may also be relevant for SUD. Since restoring this balance is thought to be necessary for antidepressant action this may also be true for the treatment of SUD.

 

It has been demonstrated that 5-HT2A receptor antagonism impairs behavioral flexibility by increasing perseveration, 5-HT2A agonism has a beneficial effect on behavioral flexibility while 5-HT1A receptors are involved in mediating the emotional state of individuals and patients with SUD.

 

As for other 5-HT1A mediated plants as being potentially cheaper options, I found the Lotus embryo at high dose was so emotionally balancing, stress buffering and took the edge of the negative and gave some bias towards more positive thinking. I'm going to have more of that as a tea fairly regularly I think.

 

[1]: https://www.tandfonline.com/…/full/10…/14737175.2016.1220834

 

Enhancing Meaning and Purpose

 

Contrary to most mental health approaches which use agents that diminish the intensity of experience, thereby allowing individuals who are otherwise overwhelmed by feelings to adequately cope and function leading to a more flattened experience of the world, can we fight rising rates of psychopathologies by bolstering individual and social sense of meaning and purpose? [1]

 

Here's a bit of the latest research working with stronger plant medicines

 

I think the making of meaning and embodying purpose is so important. What meaning do you ascribe to your life? What are you doing today that gives you meaning and purpose? Simple things like that. Today my meaning making and purpose is getting some plants to people.

 

"It makes me feel connected again. And not, flailing out there somewhere. Yeah. It's a purpose, you know? It's a purpose. And that's the whole thing is, I've been living life really without my own personal purpose ... I've– it's just been an unpurposeful life." - a study participant.

 

Several studies have demonstrated correlations between feelings of meaning in life and increased psychological well-being, increased longevity, as well as reduced risk of suicidality and depression

 

"Enhancers of meaning can be seen in the broader cultural context of late modernity's struggle to make sense and meaning of life in increasingly atomized, individualised, and stress-ridden societies."

 

In AUDs, the content of psilocybin-induced experiences has been recently studied. Experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behaviour were reported [2]. Much work is focusing on Motivational Enhancement Therapy (MET) therapy, a psychosocial treatment based on motivational interviewing, designed to build motivation through evoking the patient's reasons for change and strengthening skills to support the patient's goals around changes [3]

 

More recently, meaning-making therapy have been used as the psychotherapeutic models. The amplification of meaning automatically entails amplification of placebo. A treatment of depression currently under development will use Acceptance and Commitment Therapy.

 

Initial and still unpublished results have found significant increase in meaning in life following administration of psilocybin, as measured by the Meaning in Life Questionnaire.

 

The experience of confronting an overwhelming, ineffable, and even unfathomable quality of the world is arguably facilitated to imbue the mind and the external world with vibrant significance. By causing mental and external phenomena to appear immensely more significant, we can facilitate a reenchanted experience of the world

 

Recent studies have noted dramatic and variegated effects which include, among other phenomena, psychotherapeutic insights, creative breakthroughs, and mystical-type experiences, amplification of emotional volume and demanding that patients “face the demon.” Induction of spiritually meaningful experiences and experiences of ego dissolution, whose occurrence is often correlated with the success of therapy, but researchers have also suggested a numbers of other mediators including relational embeddness, embodiment, “the difficult struggle,” affect and catharsis, visions, and recovered sense of appropriate priorities

 

[1] https://www.ncbi.nlm.nih.gov/pubmed/29559884
[2] https://www.ncbi.nlm.nih.gov/pubmed/29515439
[3] https://www.ncbi.nlm.nih.gov/pubmed/29515449

Edited by Alchemica
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Had a good plant medicine session which made me decide to take up daily running with mindful time in nature. EE as a tool can't be discounted. While I'm used to doing brisk walks each day, a run is so much better. They're not the longest at the moment, do a sprint then walk then sprint for as long as I can to go around the block a bit. Seems even acutely, just a couple of days of it superior to brisk walks for a long time etc.

 

Why discounting exercise as a mental health aid is short-sighted

 

I think it hits self esteem really hard when you suffer from depression, anxiety or just the occasional low’

 

‘Exercise can be really intimidating because you’re forced to put yourself in front of other people doing something you may not necessarily be good at – which can obviously be really scary.

 

‘So it’s easier to sh*t on something than try doing it.


Novel approaches to alcohol rehabilitation: Modification of stress-responsive brain regions through environmental enrichment

Relapse remains the most prominent hurdle to successful rehabilitation from alcoholism. The neural mechanisms underlying relapse are complex, but our understanding of the brain regions involved, the anatomical circuitry and the modulation of specific nuclei in the context of stress and cue-induced relapse have improved significantly in recent years. In particular, stress is now recognised as a significant trigger for relapse, adding to the well-established impact of chronic stress to escalate alcohol consumption. It is therefore unsurprising that the stress-responsive regions of the brain have also been implicated in alcohol relapse, such as the nucleus accumbens, amygdala and the hypothalamus. Environmental enrichment is a robust experimental paradigm which provides a non-pharmacological tool to alter stress response and, separately, alcohol-seeking behaviour and symptoms of withdrawal. In this review, we examine and consolidate the preclinical evidence that alcohol seeking behaviour and stress-induced relapse are modulated by environmental enrichment, and these are primarily mediated by modification of neural activity within the key nodes of the addiction circuitry. Finally, we discuss the limited clinical evidence that stress-reducing approaches such as mindfulness could potentially serve as adjunctive therapy in the treatment of alcoholism.

 

Besides modulating stress hormone production in the periphery, environmental enrichment also regulates stress response by affecting central brain regions.

 

Perceiving repeated aversive events can cause one to become chronically stressed. Chronic activation of the hypothalamic–pituitary–adrenal (HPA) axis can have deleterious consequences on physiological parameters and behaviour (e.g. emotional reactivity, stereotypies, cognition).

 

Environmental enrichment is a robust paradigm which provides a non-pharmacological tool to alter stress response and seems to alter mood and things like risk of relapse.

 

Neurogenesis is stimulated by enriched environments, exercise, and learning and is inhibited by stress and aging. Even the stages of neurogenesis are influenced by these environmental factors. Enrichment and exercise stimulate the proliferation of neural stem cells

1 week of EE is reportedly sufficient to elicit increased cell proliferation and differentiation in the amygdala of adult non-drinking mice, resulting in greater numbers of oligodendrocytes and astrocytes and likely impact higher order brain regions.

Physical activity is often investigated as an easily dissociable component of environmental enrichment and elevating the level of physical activity has consistently been reported to modify behaviour, including alcohol seeking etc.

"The benefits of EE are well-accepted to be driven primarily through increased neuronal plasticity. This broadly involves alterations to the physiological properties of neurons, enhanced LTP, firing rates and network rhythms, most of which are wellcharacterised by studies of the hippocampus and cortical regions

The impact of EE on neuronal networks and region-to-region signalling could account for enrichment-mediated modifications of drugseeking behaviour, e.g. the prevention of drug-induced reinstatement attributed to the modulation of infralimbic cortex activity and reduced cue-induced reinstatement associated with increased perineuronal net intensity within the medial prefrontal cortex"

 

Edited by Alchemica
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Jokes, thats good info man : )

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Not exactly relapse prevention as such but many years ago (maybe 25ish) I worked on a program in India called The Project. which was funded to reduce the number of western junkies in India. It basically involved continually feeding opium addicts with very large amounts of Bhang, a paste made by lightly simmering cannabis, milk and spices, then pounding in a mortar and pestle. When they were too sick, we would blow charas smoke at them. It seemed to work well for those that genuinely wanted to give up.

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Not arguing with anything but also will power

 

If you are in a habit it's to be expected things may get a little interesting when you quit.

You can easily deal with it as you have a good reason to, realize that reason.

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I agree with the rake wielder on this one. There are several great tools, like CBD, that help relieve symptoms.However at the end of the day it comes down to will power. This is why terms like addict and addiction can be so problematic. They weaken your resolve by implying you are a victim.

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