RESEARCH & PUBLICATIONS

This guide summarizes decades of research into effective, evidence-based addiction treatment. It outlines the foundational principles that shape Enterhealth’s model of care.

Key findings include:

• Addiction is a chronic brain disease that alters behavior and requires long-term treatment.
• Treatment must be individualized, accounting for drug use patterns, mental health, and life circumstances.
• A comprehensive approach—including medical, psychological, and social support—is essential.
• Behavioral therapies remain a cornerstone of treatment, especially when combined with appropriate medications.
• Ongoing evaluation and flexible treatment plans improve long-term outcomes.
• Addressing co-occurring mental health disorders is critical for sustained recovery.
• Family involvement and peer support enhance engagement and accountability.

🔗 Read the full NIDA guide (PDF)

This international framework outlines a balanced, public health–centered response to the global addiction crisis—one rooted in both prevention and recovery.

Highlights include:

• Six pillars: Prevention, intervention, treatment, recovery, supply reduction, and global cooperation.
• Emphasis on prevention and recovery to reduce harm and foster long-term healing.
• Criminal justice reform integrated with evidence-based treatment and rehabilitation strategies.
• Call for individualized care across the full treatment continuum—from early intervention to re-entry.
• Focus on outcomes: Shifting from how many people enter treatment to how many sustain recovery.

🔗 Read the full Hyannis Consensus Blueprint

This clinical resource outlines evidence-based strategies to reduce relapse risk and promote long-term recovery—principles that align closely with Enterhealth’s approach to integrated treatment.

Key components include:

• Cognitive Behavioral Therapy (CBT) to recognize triggers, manage stress, and restructure harmful thinking.
• Skill-building for emotional regulation, practical life challenges, and relapse prevention.
• Medication-Assisted Treatment (MAT) to manage cravings and support mental health.
• Ongoing monitoring and regular assessments to catch early warning signs of relapse.
• Family involvement and peer support to improve accountability and long-term engagement.
• Understanding relapse as a process—emotional, mental, and physical—with intervention strategies for each stage.

🔗 View full relapse prevention report on NCBI

This randomized clinical trial examined gabapentin’s effectiveness in treating individuals with AUD and alcohol withdrawal symptoms. The study included 96 participants over 16 weeks of treatment.

Key findings include:

• Reduced heavy drinking: 27% of the gabapentin group reported no heavy drinking days vs. 9% in placebo.
• Improved abstinence rates: 18% achieved total abstinence vs. 4% in placebo.
• Stronger effect in high-withdrawal subgroup, with more pronounced benefits among those with severe prior withdrawal.
• Generally safe and well-tolerated, with dizziness as the primary side effect.

Gabapentin may be most effective for individuals with significant withdrawal history, supporting symptom-targeted pharmacotherapy for AUD.

🔗 Read the full study on JAMA Internal Medicine

This review summarizes the scope, risk factors, and treatment landscape for alcohol use disorder in the U.S., where it affects roughly 11% of the population.

Highlights include:

• High prevalence, low treatment rate: Less than 15% of individuals with AUD receive care.
• Multiple contributing factors: Both genetics and environment play key roles.
• Effective therapies include: CBT, motivational enhancement, and medication.
• First-line medications underused: Disulfiram, naltrexone, and acamprosate are FDA-approved but often overlooked.
• Promising off-label options: Topiramate and gabapentin show growing evidence of benefit.

🔗 Read full overview on PubMed

This article explores the rising crisis of stimulant use—particularly methamphetamine and cocaine—through the lens of clinical research and evolving treatment approaches.

Key insights include:

• Complex pharmacology and profound medical/psychiatric consequences.
• No FDA-approved medications yet for stimulant use disorder.
• Integrated treatment models combining behavioral therapy and emerging pharmacotherapies show the most promise.

🔗 Read the full article on stimulant use

Key insights include:

• High comorbidity: Anxiety often co-occurs with depression, increasing functional impairment.
• Long-term impact: Early-onset anxiety can persist into adulthood, affecting work, relationships, and quality of life.
• Connection to substance use: Many individuals use substances to self-medicate, leading to higher rates of addiction and relapse.
• Integrated care is essential to address both anxiety and substance use disorders effectively.

🔗 View NIMH anxiety disorder statistics

Key insights include:

• High comorbidity: Anxiety often co-occurs with depression, increasing functional impairment.
• Long-term impact: Early-onset anxiety can persist into adulthood, affecting work, relationships, and quality of life.
• Connection to substance use: Many individuals use substances to self-medicate, leading to higher rates of addiction and relapse.
• Integrated care is essential to address both anxiety and substance use disorders effectively.

🔗 View NIMH anxiety disorder statistics

A longitudinal study found that persistent cannabis use into midlife is linked to significant cognitive decline and smaller hippocampal volume—both early indicators of dementia risk.

Key findings include:

• Average IQ decline of 5.5 points from childhood to midlife.
• Impairments in learning, attention, and processing speed greater than those from tobacco or alcohol use.
• Reduced hippocampal volume among long-term users, as confirmed by neuroimaging.
• Effects persisted even after accounting for childhood IQ, socioeconomic status, and family history.

🔗 Read the full study

This randomized trial examined the risks and benefits of immediate access to medical marijuana.

Key findings include:

• Increased risk and severity of Cannabis Use Disorder (CUD), particularly in individuals with anxiety or depression.
• No significant improvement in pain, anxiety, or depression symptoms.
• Reported improvement in sleep, though further research is needed.

🔗 View full trial results

A comprehensive review of cannabis-related health risks.

Highlights include:

• CUD prevalence rising, particularly in adolescents and those with mental health disorders.
• Strong links to psychosis, depression, anxiety, and cognitive decline.
• Physical risks include cannabinoid hyperemesis syndrome, cardiovascular strain, and respiratory issues.

🔗 Read the full review

Key points include:

• Early, frequent use strongly associated with later addiction.
• Emerging THC analogs (e.g., THC-P, Δ8-THC, HHC) complicate exposure and increase potential harm.
• Widespread use of high-potency products among youth demands updated prevention strategies.

🔗 Read the full article

This narrative review outlines how cannabis use and CUD intersect with psychiatric disorders.

Highlights include:

• Strongest evidence links cannabis to psychosis.
• Mixed findings on links to mood and anxiety disorders.
• Higher CUD rates seen in those with personality disorders.

🔗 View narrative review

A large registry study showed that cannabis-induced psychosis carries the highest risk of conversion to schizophrenia among substances studied.

🔗 Read full study

A review of Colorado’s post-legalization health data revealed rising ER visits linked to cannabis, including:

• Psychosis, suicide, and pediatric exposures.
• Impaired decision-making, motor vehicle accidents, and hash-oil burns.
• Contamination risks from unregulated products.

🔗 Read full Colorado case review

A large multicenter study found:

• 6x higher risk of heart attack in cannabis users under 50.
• 4x risk of ischemic stroke, 2x risk of heart failure.
• Cannabis use is an independent risk factor for major adverse cardiovascular events.

🔗 View cardiovascular study

This study found that transcranial magnetic stimulation (TMS) significantly reduced PTSD symptoms while increasing EEG alpha power—suggesting improvements in both brain function and clinical outcomes.

🔗 Read full study

This editorial advocates for TMS to be considered a first-line treatment for moderate to severe major depressive disorder, citing strong clinical outcomes and a favorable side-effect profile.

🔗 View article

A retrospective review of active-duty Special Operations Forces personnel receiving alpha-guided rTMS showed:

Key outcomes include:

• 37% reduction in PTSD symptoms (PCL-5)
• 11% reduction in depression scores
• 45% reduction in perceived cognitive dysfunction
• Nearly half of participants with clinical depression no longer met the threshold post-treatment

The results support the safety and potential effectiveness of α-rTMS for military populations.

🔗 Read full study

This review explores the role of TMS in managing depression when standard treatments fail.

Highlights include:

• FDA-approved for major depressive disorder
• Growing body of evidence supports its efficacy for treatment-resistant cases
• Recognized as a non-invasive neuromodulation option with promising long-term data

🔗 Read article

New evidence supports targeting the frontopolar cortex for neuromodulation in addiction treatment, offering more personalized intervention strategies via TMS and MeRT.

🔗 View abstract

This randomized, double-blind trial evaluated whether adding low-dose D‑cycloserine (an NMDA-receptor modulator) could boost the effectiveness of intermittent theta‑burst stimulation (iTBS) in treating major depressive disorder.

Key findings include:

• Significantly greater symptom reduction: the D‑cycloserine + iTBS group saw a mean MADRS score drop of 6.15 points more than iTBS + placebo (Hedges g = 0.99).

• Higher remission and response rates: 73.9% in the D‑cycloserine arm had clinical response (vs. 29.3%), with no serious adverse events reported.

• Suggests D‑cycloserine may prime brain plasticity, improving outcomes when paired with TMS—but further studies are needed.

🔗 Read the full study

This comprehensive review evaluates mechanisms, patient selection, clinical effectiveness, and safety of transcranial magnetic stimulation (TMS) for major depressive disorder.

Key findings include:

• Mechanism: TMS uses electromagnetic induction to modulate neuronal activity, enhancing neuroplasticity in mood-regulating brain circuits.

• Eligibility: Best suited for patients with treatment-resistant depression who have failed medication or psychotherapy.

• Clinical Outcomes: Numerous trials support response rates up to 30–40%, with remission in a significant subset.

• Safety Profile: TMS is well tolerated, with rare serious adverse effects—low risk of seizures or fainting when protocols are followed.

🔗 Read full review on PMC

This large-scale observational study confirms the real-world effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD).

Key findings include:

• Demonstrable symptom improvement in routine clinical settings.

• Statistically and clinically significant benefits reflected in quality of life and functional status gains.

• Offers robust support for rTMS as a viable non-invasive treatment option beyond controlled clinical trials.

🔗 Read the full PubMed summary

This review explores the experimental use of repetitive transcranial magnetic stimulation (rTMS) to address cravings and substance use across addictions including nicotine, alcohol, cocaine, and methamphetamine.

Key findings include:

• 19 human studies involving 316 participants showed promise in reducing craving and substance use.

• Tobacco and cocaine studies reported reduced nicotine and drug intake in controlled trials.

• Mechanisms may involve dopamine/glutamate modulation and improved control of cue-induced behavior via the dorsolateral prefrontal cortex.

• TMS in addiction remains investigational, but early data support its potential within integrated treatment programs.

🔗 Read full review on PMC

This expert analysis proposes a new model pairing TMS with psychotherapy (TAP), aiming to leverage enhanced neuroplasticity through brain stimulation and integrate it within a broader therapeutic framework.

Highlights include:

• TMS is “physiological psychotherapy”: Modulates brain network activity to restore more natural brain states.

• Dynamic causal modeling identifies precise brain circuits for individualized targeting.

• Three-phase TAP framework: Pre-treatment planning, in-session support, and post-treatment consolidation—designed to support lasting change.

• Early-stage but promising discussion on how TMS may enhance self-reflection, emotional insight, and growth when combined with psychotherapeutic modalities.

🔗 View full article on Psychology Today

This double-blind, sham-controlled trial introduced Stanford Neuromodulation Therapy (SNT)—an accelerated, connectivity-guided intermittent theta-burst stimulation (iTBS) protocol for treatment-resistant depression.

Key takeaways include:

• ∼90% remission rate after just 5 days of active SNT vs. ~13% with sham treatment.

• Mean MADRS score reduction of 52.5% for active treatment vs. 11.1% in sham.

• Treatment targets left dorsolateral prefrontal cortex regions most anticorrelated with subgenual anterior cingulate cortex, maximizing personalization.

• Results suggest that accelerated, personalized TMS protocols could substantially outperform standard iTBS—pending more long-term durability research.

🔗 View full study on American Journal of Psychiatry

This review examines the use of transcranial magnetic stimulation (TMS) as a potential therapy for anxiety disorders, including generalized anxiety disorder, panic disorder, and PTSD.

Key insights include:

• TMS shows promise in reducing anxiety symptoms across several small-scale clinical trials.

• It may serve as an alternative or adjunctive option when psychotherapy or medications are insufficient.

• Research is early-stage, and further high-quality trials are needed to confirm efficacy and optimal protocols.

🔗 Read the full review

Key findings include:

• Evidence supports improved cognitive outcomes (e.g., memory, attention), symptom relief (e.g., headaches, sleep disturbances), and functional gains following treatment.

• Studies show 13 of 14 mTBI cases reported measurable benefit across various neurocognitive and daily function metrics.

• While results are promising, responses vary—particularly in cases of diffuse axonal injury—indicating not all patients respond equally.

• Neuromodulation remains investigational in TBI rehab, though early data suggest positive impact on recovery trajectories.

🔗 Related meta‑analysis on TBI neuromodulation 

This study used spectral dynamic causal modeling (spDCM) and resting‑state fMRI to investigate how repetitive transcranial magnetic stimulation (rTMS) affects emotional well‑being in patients with chronic traumatic brain injury (TBI).

Key findings include:

• Reduced excitatory and increased inhibitory connectivity in specific cortico-limbic circuits, notably involving the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), and anterior insula.

• These shifts in effective connectivity were associated with improved emotional regulation, supporting rTMS as a tool to recalibrate dysregulated brain networks in TBI.

• Implicates DLPFC-targeted rTMS as a mechanism for restoring balance in emotion-regulatory neural pathways.

🔗 Read full study on Molecular Psychiatry

This symposium-based review unveils how key neuromodulators—particularly norepinephrine, dopamine, and acetylcholine—regulate brain oscillations, sleep architecture, sensory responsiveness, and memory consolidation during non-REM sleep.

Key insights include:

• Neuromodulator levels (NE, DA, ACh) don’t simply drop during sleep—they fluctuate in rhythms that structure sleep microstates and support memory processing.

• These oscillatory patterns orchestrate the timing of neuronal events such as spindles and sharp-wave ripples, crucial for memory consolidation.

• Altered neuromodulatory signaling and disrupted sleep architecture are implicated in psychiatric and neurodegenerative disorders.

🔗 Read the full review on PMC

Oxidative stress plays a central role in the development of depression, interacting with neuroinflammation, mitochondrial dysfunction, and neurotransmitter imbalance.

Key insights include:

• Antioxidant interventions—like omega-3s, exercise, probiotics, and antidepressants—may help restore balance.
• Targeting oxidative stress, inflammation, and mitochondrial health together can support both mood and recovery from addiction.
• Patients with high oxidative stress may have lower omega-3 levels, linking diet directly to mood symptoms.

🔗 Read study on oxidative stress and depression
🔗 Omega-3 and depressive symptoms study

A healthy gut microbiome influences brain function and emotional well-being via neurotransmitter production and immune modulation.

Highlights include:

• Short-chain fatty acids from fiber-rich diets positively affect mood and inflammation.

🔗 SCFAs & gut-brain axis study

• Dysbiosis (gut imbalance) is linked to depression and cognitive issues.

🔗 Dysbiosis and depression review

• Gut microbes aid in nutrient absorption critical for mental stability.

🔗 Gut-brain communication review

Certain vitamins and minerals are essential for brain health and may alleviate depression, anxiety, and stress-related symptoms.

Notable findings:

• Vitamin B3 (niacin): Case studies suggest potential benefits for alcoholism and mood stabilization.
  🔗 Read: Vitamin B3 & alcoholism case series
• Vitamin B6: Linked to reduced anxiety and visual sensory processing improvements.
  🔗 Study: High-dose B6 and anxiety
• Vitamin B12: Deficiency tied to fatigue, depression, memory loss, and even psychosis.
  🔗 Study on depression and B12

Gut microbes help regulate mood, immunity, and neurotransmitter synthesis—key factors in addiction vulnerability and recovery.

Core takeaways:

• Obesity, inflammation, and mental health may all be linked via microbiome disruptions.
• Microbiota influence cravings, mood, and impulse control.

🔗 Gut microbes & energy balance
🔗 Inflammation & metabolic disorders

NAC, a precursor to glutathione, has strong anti-inflammatory and antioxidant properties with growing support in psychiatry.

Applications include:

• Adjunctive treatment for depression, schizophrenia, OCD, and SUD.
• Reduces cravings and withdrawal symptoms by modulating glutamate and inflammation.

🔗 Review of NAC’s psychiatric use

Systemic inflammation is increasingly recognized as a shared feature of many mental health disorders.

Key associations:

• Elevated inflammation in depression, anxiety, PTSD, bipolar disorder, and schizophrenia.
• Treating root causes—like poor diet, infections, or toxin exposure—may improve outcomes.

🔗 Meta-analysis on inflammation & mood disorders
🔗 CRP & bipolar meta-analysis
🔗 Schizophrenia & IL-6 analysis

Amino acids are precursors to key neurotransmitters and play a vital role in detox, especially in patients with addiction-related liver damage.

Highlights include:

• Branched-chain amino acids can help manage hepatic encephalopathy and support cognitive function.
• Amino acids like tryptophan, tyrosine, glutamate, and GABA are essential for mood, reward, and impulse control.

🔗 Review on amino acids in liver therapy
🔗 Study on amino acid excess and neurotransmission

Sleep issues are common in those with SUDs and can worsen relapse risk.

Key points:

• Substance users are 5–10x more likely to suffer from sleep disorders.
• MeRT may normalize disrupted brainwave activity, improving sleep regulation and comorbid conditions like PTSD or depression.
• Functional psychiatry addresses root causes like cortisol imbalance, melatonin deficiency, and nutrient depletion.

🔗 Sleep disorders & substance use study

This narrative review explores how poor nutrition and nutrient deficiencies can negatively impact recovery from substance use disorders (SUD), including opioid addiction.

Key findings include:

• High prevalence of malnutrition in individuals with AUD and DUD, contributing to both physical and mental health challenges.
• Deficiencies linked to anxiety, depression, myopathy, and bone loss.
• Shared reward pathways between food and substances may cause “addiction transfer” during recovery.
• Improving nutritional status may reduce cravings, improve mood, and enhance recovery outcomes.

🔗 Read study 1 (Addictive Behaviors)
🔗 Read study 2 (Drug and Alcohol Dependence)