You wake up and peek over at your to-do list. Today is Sunday which means it’s laundry day and cleaning day. Where to start? The thick coat of clothes scattered across your bedroom floor seems… overwhelming. You start there, by sorting them into piles of dirty versus clean.
Though, if they’ve been crawling on your carpet for over a week, shouldn’t they also be washed? Change of plans. You start sorting the clothes by color because they’ll all be going into the wash. Then a brilliant idea pops into your head. Why not organize your closet by color? Lightest clothes on the left, darkest on the right.
Should you wash everything first or organize the clothes already in your closet? Let’s organize first, let’s ‘get it over with’. You start by throwing all of your closet apparel onto your bed. Done. But wait, if you’re organizing by color, your hangers should also be in accordance with the color scheme, and right now, 5 of your hangers are wooden, 10 are those are from your local laundromat—made of wire and bent out of shape, and the rest are some mismatched plastic hangers that never fail to make your clothes slip off and end up on your closet floor.
You can’t organize your closet without new, color-coordinated hangers. To the home goods store you go. You grab your bag, phone, wallet, and you’re out the door. You reach for your car door handle then realize you forgot your keys inside. Here comes that sigh of disappointment, the one that inevitably ensues after every effort to establish structure and focus into your life.
The to-do lists, the post-it notes on your desks, the pile of journals you’ve bought to write form into your routine, swaddled in between those books you’ve collected, but only read a few pages of on the day you purchased them. Compensating for your lack of direction is tiring, it’s shameful, it’s easier said by every family member and motivational speaker, than actually done.
This is attention-deficit hyperactivity disorder (ADHD). Notorious for causing a lack of focus and bouts of impulsivity, the reverberations of ADHD are much more far reaching than we’re used to narrating. They are deeply pervasive to the daily lives of over 2.4 million children aged 6-11 years old in the United States, and to the 0.96% of American adults diagnosed with this disorder in our country, as of 2019.
Common treatments for this disorder include stimulant prescription medications like Adderall and Concerta, but their side effects introduce a whole new world of complications like severe difficulties with sleep and an unhealthy suppression of appetite. Not to mention its high potential for abuse and addiction. Hence, it’s unsurprising why sufferers of ADHD are looking to uncover alternative ways to subdue their symptoms without confinement to such inhibiting side effects.
Today we’ll be discussing the potential therapeutic role of psychedelics in helping those with ADHD come to a more tethered sense of self. To the best of our knowledge, this is the first comprehensive meta analysis conducted and publicly published on the topic, from a neuropsychopharmacological stance.
To preface, MindMed, a biotech company helping to develop psychedelic therapeutics, is currently in phase 2a of LSD trials for the treatment of adult ADHD. However, since clinical trials are still ongoing, findings remain unclear.
By summarizing what is currently understood about the neurological underpinnings of ADHD, and synthesizing that with the already-known effects of psychedelics on the brain, we may be able to accurately hypothesize these drugs’ mechanisms of action on ADHD brains, perhaps with enough accuracy to predict outcome measures of these clinical trials. If you read through to the end of this article, we’ll also be reviewing the anecdotal reports of our survey respondents, who’ve used psychedelics to keep their ADHD symptoms at bay. Their testimonials may also be a great indicator of clinical trial findings.
ADHD In The Brain
In a 2017 study conducted by Jean-G. Gehricke et al. 71 participants were recruited, 31 of which had ADHD, and 41 of which didn’t- serving as control figures for the study. Using MRI scans on every participant, researchers were able to compare differences in brain images between each group.
To identify the significance of anatomical variability within group and between group, voxel-wise linear models were employed. This method allows one voxel, or one unit of the brain imagining graphics, to be analyzed independently, as means of assessing if any combination of individual regression measures could be used to singulate a score that accurately predicts an ADHD diagnosis.
Results indicated that participants with an ADHD diagnosis demonstrated reduced size and connectivity in the occipital lobe, the superior temporal gyrus, right postcentral gyrus, basal ganglia, left posterior insula, orbito-medial prefrontal cortex, superior parietal cortex (contributing to the temporo-parietal junction), and in the cingulum. Cortico-limbic circuitry, connecting the amygdala with the thalamus and orbital frontal cortex, also demonstrated significant disruption of connectivity.
This disruption contributes to widely-known ADHD symptoms of impaired decision making and impulsivity. In the ADHD group, the hippocampus (associated with learning and memory) was significantly enlarged compared to the control group. Those with inattentive symptoms were found to experience medial enlargement, while those with hyperactive symptoms showed a more lateral enlargement.
Another study conducted in 2016 by Richard B. Silberstein et al., recruited 43 male participants recently diagnosed with ADHD and who had not been previously medicated with any stimulant prescription drugs. The control group included 25 males that did not have ADHD. Though the study sought to understand the effects of a methylphenidate dose on brain functional connectivity, its results tell us a very enticing story.
Participants conducted cognitive tasks on a computer monitor while researchers recorded brain electrical activity to determine correlations in brain function. The statistical significance of these correlations were determined by the threshold r value corresponding to p ≤ .01. Results found that methylphenidate reduces DMN (Default mode network) activity in the brain, allowing enhanced focus on task-related objectives. The DMN is activated in absence of our focused attention onto our outer environments, it’s active when we daydream of the future or almost-subconsciously replay images of the past, and is less active when we’re engaged in a cognitive task.
Now, what we take from this study is key in understanding the biomarkers of ADHD. In people with ADHD, the DMN is overactive. It draws our sustained attention away from outer-attentional tasks with intrusive, ruminating thoughts that are unrelated to a task’s objective. Therefore, it’s evident why a drug that suppresses ruminating thoughts or overactivity of the DMN, would be helpful in enhancing focused attention skills in those with ADHD.
One of the most predictive biomarkers of ADHD is low levels of norepinephrine, also known as noradrenaline, in the brain. The scarcity of this neurotransmitter is largely at fault for causing difficulty with focus in those with ADHD.
A 2019 study led by Christine Ulke and colleagues, recruited 20 ADHD patients to study the hypothesis that NET (norepinephrine transporter) availability is altered in people with ADHD. Through employment of questionnaires like the Conners’ Adult ADHD Rating Scale, measures like the Test of Attentional Performance (TAP), and use of electroencephalography, researchers compared neurological data to that of a control group. Findings revealed a significant negative correlation (p = .003) between mean DVR scores in attention-related factors and NET availability, meaning higher ADHD symptom severity is proportional to lower levels of norepinephrine.
Psychedelics In The Brain
To bring all of our research together, we explore a 2018 study conducted by Katrin H Preller and colleagues on the modulations of brain connectivity in LSD-induced states. Researchers recruited 24 healthy participants in a double-blind, placebo-controlled study. Baseline data was collected on resting-state functional connectivity and later compared to post-experiment data of placebo (ketanserin dose) participants and the test group (LSD dose).
Though the study’s aim was to implicate 5-HT2A (serotonin) receptors in LSD’s neuropharmacology, its methods of deduction were able to pinpoint the brain regions that were affected by LSD and the orientation of those effects. Findings indicated that LSD induces hyper-connectivity in the occipital cortex, superior temporal gyrus, postcentral gyrus, medial and lateral prefrontal cortex, the cingulum, insula, cingulum, and the temporoparietal junction. Increases in connectivity were also noted in the anterior and posterior cingulate cortex, the thalamus, amygdala, and the basal ganglia.
A 2015 study conducted by Palhano-Fontes et al., researchers recruited 10 participants to study the effect of ayahuasca, a hallucinogenic drug that contains 5-HT2A (serotonin) receptor agonists, on DMN connectivity. Using fMRI protocols, the study found that the DMN experienced a significant decrease in activity.
This same decrease in DMN activity was observed in a 2013 study conducted by Muthukumaraswamy et al. Using magnetoencephalography, researchers monitored the brain electrical activity of healthy participants who were dosed with an intravenous infusion of psilocybin. The study’s primary finding was a significant decrease in oscillatory power within the DMN, indicating reduced activity in that brain region.
On DMN modulation by psychedelic drug, LSD, a placebo-controlled, cross-over study was run in 2018 by Felix Muller and colleagues. 20 healthy participants were recruited. The study found that acute administration of LSD (100 μg) significantly (p < 0.005) reduced visual, sensorimotor, and auditory network connectivity within the default mode network.
Ketamine, a dissociative anesthetic, has been found by Kubota et al. in 1999, as well as Lopez-Gil et al. in 2019, to increase norepinephrine (NE) efflux in the mPFC while inhibiting its reuptake, allowing for more NE to be at the brain’s overall disposal.
Curiously, LSD was not shown to inhibit NE reuptake by Dengler et al. in 1961. After consumption of LSD, Hollister and Moore found no alteration to urinary excretion of NE, in 1967. In fact, a study led by David Peters in 1974, found that administration of LSD over a period of 14 days decreased NE levels by 20% in the brainstem.
Psilocybin however, was found to transiently increase NE synthesis in the brain, with normetanephrine (a byproduct of NE) increasing more than double after 1 hour of psilocybin consumption. Not only does psilocybin stimulate the production of extrasynaptic NE, but it also affects turnover, insinuating prolonged and sustainable change to NE modulating systems (Stolk et al., 1974). A 2016 study by Rickli et al. agrees with these findings, concluding that psilocybin inhibits NE reuptake by binding to NE transporters.
Psychedelics on ADHD
From the studies we’ve reviewed, much can be inferred about the treatment potential of psychedelics for ADHD. As we’ve noted, Gehricke’s study mentions a reduction of size and connectivity in several ADHD brain regions, nearly all of which have demonstrated increased size and connectivity after intake of LSD in Preller’s study.
Most pressingly, increased connectivity between the amygdala and thalamus is correlated to an enhancement in memory processing, decision making, and emotional responding, such as increased motivation. The thalamus is our brain’s information relay system and the amygdala detects threats and activates fear responses to stimuli. Increased connectivity in these regions would thus increase the likelihood of more appropriate amygdala activations and consequent thalamus relays, where those with ADHD naturally experience a reduction of their communication which contributes to symptoms of inattention.
Gehricke’s research also found enlargement of the hippocampus in the ADHD group. To understand how psychedelics could aid this inflammation, we take a look at some more research. A 1999 study conducted by E Gould et al., explains that hippocampal neurogenesis occurs with the formation of new neurons, effectively modulating its circuitry.
A 2015 study led by Gerd Kempermann and colleagues, also indicates that adult hippocampal neurogenesis originates from the existence of new cells, whose dendritic spines and axons extend into the CA3 area of the hippocampus, allowing for better connectivity and reduced inflammation. In a 2021 study conducted by Ling-Xiao Shao et al., we find that a single dose of psilocybin sustainably increases the number and size of neuronal connections by 10% through neurogenesis.
Thus, psilocybin and other serotonergic psychedelics demonstrate strong potential for reducing the hippocampal inflammation associated with ADHD by promoting synaptic plasticity. In those diagnosed with ADHD, short-term memory loss is one of the most frustrating symptoms of the disorder. This psychedelic-induced reduction in hippocampal inflammation and enhancement of connectivity would thus likely result in improved memory acquisition and recall.
Silberstein’s study found that adults with ADHD experience overactivity in the DMN, a major culprit of reduced task-oriented focus and increased rumination. The research of Palhano-Fontes, Muthukumaraswamy, and Felix Muller prove that serotonergic psychedelics like ayahuasca, psilocybin, and LSD, reduce activity in the DMN. Indicating an effective reduction in ruminating thoughts and daydreams which typically distract from cognitive tasks presented to people with ADHD.
Though LSD appears to decrease or have no effect on NE levels, other drugs like ketamine, and especially psilocybin, have been proven to increase NE levels sustainably. As we know, people with ADHD suffer from a lack of NE which contributes to symptoms of poor focus and inattention. Thus, a drug like psilocybin, which increases NE levels, may be an extremely viable therapeutic option for combating this natural NE depletion and restoring NET function to the brain.
How Can Psychedelics Be Used To Treat ADHD?
With such encouraging research outcomes, our appetite to treat ADHD symptoms must surely be on the rise. But what are the logistics of treating ADHD with psychedelics, what substance should you choose, and does this mean you have to be tripping every single day?
To ease your mind, no. You do not have to, and frankly you should not be tripping every day, under any circumstance. However, there are several ways to go about creating a treatment plan. First, understand that psychedelics are not prescriptive. As a society we’re so accustomed to the westernized approach of prescriptive pharmaceutical protocols that we’ve become desentized to the tune of our own bodies. Some even find it more comforting to take on these one-size-fits all medical approaches because it permits us to release personal accountability over our own health.
Psychedelics don’t work this way. A therapeutic psychedelic experience requires intention and purpose, a keen ear to the voice of our bodies, and active efforts to curate an outer environment that reflects our most productive and satisfied inward landscapes.
Having said that, there are a couple of options for harnessing the therapeutic potentials of these medicines and they all fall on a spectrum, with microdosing on one end, and macrodosing on the other. A microdose is a small, sub perceptual dose of a psychedelic. You can drive, operate heavy machinery, and have full physical competency while on a microdose.
A microdose can be used as a maintenance procedure to keep up behavioral momentum after a larger, macrodose experience. It can also be used as a way to taper off of medications like adderall or concerta, and SSRIs, so the psychedelic compensates for the depletion of serotonin or stimulation that comes almost immediately after discontinuation of pharmaceutical drugs. A microdosing regimen can be adopted at any time when you’d like to reap all of the aforementioned benefits of psychedelics for treating your ADHD.
Another option is to embark on a macrodose psychedelic experience. This larger-dose trip brings with it all of the expected hallucinatory effects. A macrodose is a great way to gain these benefits in a much more rapid fashion. Many see it as a ‘reset’ that catalyzes potent behavioral and neurological change from that point forward.
Many feel that a one macrodose session is all they need to maintain positive change for a long period of time. Others prefer to microdose for a more stable and systematic enhancement of neurological functioning.
In terms of which substance would be best to treat ADHD with, that choice is completely up to you. However, if we’re strictly deriving a conclusion from the findings of each study we reviewed, LSD and psilocybin seem to be the top contenders. Psilocybin may be of amplified benefit for this specific disorder because of its ability to increase NE availability in the brain, but as of now, there is more scientific research supporting LSD for improved connectivity of specific ADHD-related connectivity dampers.
In preparation for this analysis, we surveyed a community of psychedelic users who also have ADHD. We asked them to describe their experiences treating this disorder with psychedelics. Of the 66 people reached, we’ve compiled a list of responses that received the most user approvals.
“I have ADHD and I have found that 100 mg of dried Cubes is more valuable to me than methylphenidate ever was.” – Survey Respondent
“250 mg of mushrooms in a capsule with my morning tea works better than ADHD medication ever did. I do (microdose) Monday-Thursdays on and weekends off basically. I grind up whole mushrooms and make my own capsules. In a 00 size capsule I can fit around 250 mg on average and I’ve found that’s the perfect dose before the come up bothers me at work. Helps me focus and control my appetite/munchies…It’s just what I find works best for me, perfect balance of being calm but productive.” – Survey Respondent
“Combined with therapy and mindfulness practice, it’s absolutely changed my life. Psychedelics were the catalyst to find a therapist and get my life right!… It’ll be a lifelong journey and though I (still) often find myself getting frustrated and angry at stupid things, or being mean to myself, it’s easy to get back on track and choose to be lighter. Would recommend it to everyone.” – Survey Respondent
“I have ADHD and have done some microdosing and one macrodose. The big thing for me is feeling present; I often feel like my brain is constantly pulling me in several directions at once, and it can be hard to feel comfortable in that. The macro dose was incredible and for the next ~3 days I feel more present and calm than I ever had in my entire life. I felt like I could actually settle on thoughts and there was a deliberateness to reality that I didn’t feel before. Slowly faded over the course of ~ 3 weeks, but there were still impacts.
Microdosing tends to be somewhat helpful, but similarly to other medications it doesn’t solve the problem, but grants the ability to focus significantly more than before. I find that methylphenidate is hard to beat, but microdosing definitely helps a lot. I usually use it for long days of social interaction, to combat restlessness and help me focus on other people more, be present, and listen… Hope this helps!” – Survey Respondent
“Honestly when I was peaking on 500ug (of LSD) during my most recent trip it felt like my ADHD and anxiety disappeared. It was like I was still myself, but just a basic fundamental version of what it means to be me. My attention and awareness felt so present, as if I was fully connected and embodied in each moment.” – Survey Respondent
From the literature reviews we’ve conducted today and anecdotal reports on the use of psychedelics for treatment of ADHD, it can be accurately deduced that serotonergic psychedelics like LSD and psilocybin offer great therapeutic potential for managing this disorder. As we await the results of ongoing clinical trials, this analysis may be helpful in kick starting the psychedelic-ADHD conversation.
Much more research is needed to scientifically confirm the treatment premise we’ve laid out today, but all roads seem to point to a very promising future for psychedelics in our mental health pharmacopeia. The information provided today serves purely for educational purposes and should not be taken as medical advice. As always, proceed with what feels comfortable and authentic to you and your personal healing journey.
We understand that traversing such unfamiliar grounds can be tricky, especially when excitement is so high for these up-and-coming treatments. Here, at Psychedelic Passage, we facilitate therapeutic psychedelic experiences in every state across the U.S., both for macrodosing and microdosing purposes. If you feel our services may be of benefit to you, we encourage you to book a consultation with us today.
Our experienced facilitators are eager and more than equipped to answer all of your psychedelic-related questions. If you’d like to conduct some more research on the vast applications of psychedelic medicines, we suggest taking a peek at our blog page, where you’ll find a curated library of resources for satiating all of your psychedelic curiosities. Well friends, that’s all for now. We hope this review will serve as a skeletal foundation for future studies, one that can be built off and amended as more research comes to surface. Safe journeying!