Psychedelics as Treatment for Depression in Patients with Dementia

Literature Review


Older adults

Aging is an inevitable part of life. Approximately 20% of the population in developed countries is comprised of adults over 60 years old (Wick, et al., 2000). The average life expectancy continues to grow meaning the risk of an individual developing an age-related disease also continues to grow (Clarfield, 2017). Future research should investigate how to prevent or cure age-related diseases.


Depression in older adults.

The American Psychiatry Association (APA) defines major depressive disorder as when at least five of the following nine symptoms are present: sadness, disinterest, weight changes, sleeping pattern changes, delayed cognition, tiredness, self-loathing, inability to concentrate, or reoccurring thoughts of suicide (2013a). Depression is not a normal part of getting older, although aging increases the risk of an individual developing depression (Blazer, 2003). Depression in older adults should be treated as any other mood disorder because complications may arise if the depression is left untreated. The Geriatric Depression Scale (GDS) serves to quantify the severity of depression in older persons by assessing mood, self-esteem, and energy (Sheikh & Yesavage, 1986). The shorted version of the GDS is used for patients with poor attention-spans such as those with dementia. This scale is not specifically for older persons with cognitive impairment. Consequently, it may not be a completely accurate assessment for patients with dementia.


Dementia in older adults.

Dementia can be the result of several medical conditions such as Alzheimer’s disease, Parkinson’s disease, and Lewy-body dementia (Gale, Acar, & Daffner, 2018). The World Health Organization estimates that 50 million people live with some form of dementia with 60-70% of cases attributed to Alzheimer’s disease (World Health Organization [WHO], 2019). Slightly different symptoms are present depending on the disease. The APA defines dementia as a neurocognitive disorder diagnosed when the following symptoms are present: poor attention-span, mal-orientation, fluctuation in disturbances, cognitive decline, and evidence of a physiological cause (2013b). The Global Deterioration Scale (GDS) defines stages that correlate with the severity of a patient’s cognitive decline by assessing memory, mood, behaviors, and activities of daily living (Reisberg, et al., 1982). Severe cognitive decline significantly decreases a person’s quality of life and complicates preexisting mental disorders. The comorbidity of dementia and depression can have severe and complex outcomes.


Depression and dementia.

Depression in older adults is a strong indicator of the early stages of dementia (Kaup et al., 2016). The symptoms of depression often continue while the dementia disease progression. An estimated 10-30% of people living with dementia also suffer from depression (Devanand et al., 1997). The Cornell Scale for Depression in Dementia (CSDD) scores the severity of depression specifically for patients with dementia by assessing mood-related signs, behavioral disturbances, physical signs, cyclic functions, and ideational disturbances (Alexopoulos, et al., 1988). The combination of depression and dementia often manifests into agitation and hostility (Volicer, 2018). These behaviors can make it difficult for caregivers to provide proper care to older adults suffering from both depression and dementia. Trials of antidepressants are currently the recommended treatment for older adults with depression and dementia despite the high risk of adverse effects (Ford & Almeida, 2017). A new depression symptom-relief medication could allow caregivers to provide proper care without the adverse effects of current antidepressants.


Psychedelics

Psychedelics are a class of drugs that increases serotonin levels and consequently alters mood, perception, and cognitive processes (Nichols, 2016). The side-effects of increased serotonin levels make psychedelics desirable to some people. Psychedelics are commonly consumed either religiously or recreationally (Luna, 2011), but small doses can improve cognitive abilities (Prochazkova et al., 2018). Future research may reveal the full potential of using psychedelics to treat mood disorders. The general use of psychedelics is controversial: some religious groups view psychedelics as a way to enhance their spirituality (Luna, 2011) while other religious groups condemn all recreational drug use (McNamara, 2011). This is the basis for the debate on the legality of psychedelics. Many countries, including the United States, classify psychedelics as illegal controlled substances (United States Code, 2016). Research is greatly limited due to the legal status of psychedelics.


History.

Some American religious groups in the early twentieth century encouraged the association of drugs with immoral behaviors (McNamara, 2011). The Harrison Anti-Narcotic Act of 1914 constitutionally enabled the federal government to regulate controlled substance (Terry, 1915), state legislations began classifying psychedelic-related crimes as felony offenses in 1966 (Lee & Shlain, 1987), and the 1970 Control Substances Act categorized psychedelics as schedule I drugs (United States Code, 2016). All of this legislation restricted the accessibility of psychedelics. Additionally, controlled substances with no medicinal benefit and a high risk for abuse are classified as schedule I drugs (United States Drug Enforcement Administration [DEA], n.d.), so psychedelic research was significantly reduced for a few decades (Carhart-Harris & Goodwin, 2017). The United States Drug Enforcement Administration (DEA) significantly increased the approval rate for research regarding schedule I drugs in 2017 (2018). The increased accessibility to psychedelic research could develop clinical use for medicinal benefits.


Dimethyltryptamine (DMT).

DMT is a psychedelic associated with strong hallucinogenic effects (Cakic, Potkonyak, & Marshall, 2010). Some people recreationally use DMT for a powerful psychological experience with a low risk of adverse effects (Davis, et al., 2018). The production of the spiritual brew, ayahuasca, commonly includes the plant

Psychotria viridis

which contains DMT (Domínguez-Clavé et al., 2016). Ayahuasca has been used in religious ceremonies throughout the upper Amazon for centuries (Luna, 2011). This sacred view of DMT’s psychological effects suggest a higher benefit to risk ratio.

Case studies have shown that, while uncommon, DMT can induce psychosis (Dobkin de Rios & Rumrrill, 2018) (Paterson, Darby, & Sandhu, 2015). The possibility of dramatic adverse effects is reason to proceed research with caution. Many observational studies have been conducted to investigate the current uses of DMT. A fewer number of controlled experiments have been performed to directly test the effects of DMT in a monitored setting.


Microdosing psychedelics for depression.

The term

microdosing

refers to the regularly scheduled consumption of very small dosages of some drug. Microdoses of psychedelics are typically ten to twenty times smaller than a recreational dose (Kuypers, et al., 2019). A microdose is usually too small to cause noticeable hallucinogenic effects. The microdose will cause an increase in serotonin levels resulting in some less intense side-effects. Approximately 20% of microdosers have experienced some acute adverse effects (Hutten, et al., 2019). The risks and benefits of any drug must be assessed before clinical usage. Microdoses of DMT had an antidepressant effect on rats without increasing anxiety (Cameron, et al., 2019). This evidence suggests that microdoses of DMT could be used clinically to ease symptoms of depression.

Current antidepressants may take up to several weeks before becoming fully effective (Otte et al., 2016). Waiting several weeks for symptom relief may feel distressing for a person with depression. Additionally, the first antidepressant trial fails for about 30% of depression cases leading to a long trial-and-error period (Conway et al., 2017). Being subjected to many failed medications may be disheartening for people suffering from chronic depression. Ayahuasca can be utilized as a fast-acting medication for treatment-resistant depression (Palhano-Fontes et al., 2019). Utilizing psychedelics as antidepressants could change the way psychiatrists treat depression.


Psychedelics effect in older adults.

There is not much evidence that psychedelics are beneficial specifically for older adults. Small doses of cannabis do not cause any significant effects in older adults with dementia (Van den Elsen, et al., 2015). The absence of any results includes the absence of adverse results. The clinical use of psychedelics has proven to be safe enough to begin research with larger doses.


Current Study

The recent increase in studies concerning the medicinal benefit of psychedelics could lead to a breakthrough in how depression is treated. This potential medication could also be useful in specifically treating depression in older adults with dementia. This experimental study explores the direct effect that microdoses of DMT have on treating depression in older adults with dementia. Prior studies suggest that microdoses of DMT can relieve symptoms of depression (Cameron, et al., 2019) (Palhano-Fontes et al., 2019). Some case studies warn researchers of the risk of psychedelic induced psychosis (Dobkin de Rios & Rumrrill, 2018) (Paterson, Darby, & Sandhu, 2015). Another study demonstrated the low risk of adverse effects of microdoses of psychedelics in older adults with dementia (Van den Elsen, et al., 2015). These studies together suggest the potential benefit of microdoses of DMT on depression symptom relief for older adults with dementia.


References

  • Alexopoulos, G.S., Abrams, R.C., Young, R.C., & Shamoian, C.A. (1988). Cornell Scale for Depression in Dementia.

    Biological Psychiatry

    ,

    23

    (3), 271-284. doi: 10.1016/0006-3223(88)90038-8
  • American Psychiatry Association [APA]. (2013a).

    Diagnostic and statistical manual of mental disorders

    , (5th ed.). Depressive Disorders. doi: 10.1176/appi.books.9780890425596.dsm04
  • American Psychiatry Association [APA]. (2013b).

    Diagnostic and statistical manual of mental disorders

    , (5th ed.). Neurocognitive Disorders. doi: 10.1176/appi.books.9780890425596.dsm17
  • Blazer, D.G. (2013). Depression in Late Life: Review and Commentary.

    The Journals of Gerontology: Series A

    ,

    58

    (3), M249-M265. doi: 10.1093/gerona/58.3.M249
  • Cakic, V., Potkonyak, J., & Marshall, A. (2010) Dimethyltryptamine (DMT): Subjective effects and patterns of use among Austrailian recreational users.

    Drug and Alcohol Dependence

    ,

    111

    (1-2), 30-37. doi: 10.1016/j.drugalcdep.2010.03.015
  • Cameron, L.P., Benson, C.J., DeFelice, B.C., Fiehn, O., & Olson, D.E. (2019). Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents.

    ACS Chemical Neuroscience

    ,

    10

    (7), 3261-3270. doi: 10.1021/acschemneuro.8b00692
  • Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N,N-Dimethyltryptamine.

    Brain Research Bulletin

    ,

    126

    (Pt. 1), 74-88. doi: 10.1016/j.brainresbull.2016.04.016
  • Carhart-Harris, R. L., & Goodwin, G. M. (2017). The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future.

    Neuropsychopharmacology

    ,

    42

    (11), 2105-2113. doi: 10.1038/npp.2017.84
  • Clarfield, A.M. (2018). Healthy Life Expectancy Is Expanding.

    Journal of the American Geriatrics Society

    ,

    66

    (1), 200-201. doi: doi.org/10.1111/jgs.15165
  • Conway, C. R., George, M. S., & Sackeim, H. A. (2017). Toward an evidence-based,operational definition of treatment-resistant depression: when enough is enough.

    JAMA Psychiatry

    ,

    74

    (1), 9–10. doi: 10.1001/jamapsychiatry.2016.2586
  • Davis, A.K., Barsuglia, J.P., Lancelotta, R., Grant, R.M., & Renn, E. (2018). The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption.

    Journal of Psychopharmacology

    ,

    32

    (7), 779-792. doi: 10.1177/0269881118769063
  • Devanand, D. P., Jacobs, D. M., Tang, M., Castillo-Castaneda, C., Sano, M., Marder, K., … & Stern, Y. (1997). The Course of Psychopathologic Features in Mild to Moderate Alzheimer Disease.

    Archives of General Psychiatry

    .

    54

    (3): 257–263. doi:10.1001/archpsyc.1997.01830150083012
  • Dobkin de Rios, M. & Rumrrill, R. (2008). A Hallucinogenic Tea, Laced with Controversy: Ayahuasca in the Amazon and the United States. Westport, CT: Praeger.
  • Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J.C., Álvarez, E., de la Fuente Revenga, M., … Riba, J. (2016) Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

    Brain Research Bulletin

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    126

    (Pt. 1), 89-101. doi: 10.1016/j.brainresbull.2016.03.002
  • Ford, A. H. & Almeida, O. P. (2017). Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?

    Drugs & Aging

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    34

    (2), 89-95. doi: 10.1007/s40266-016-0434-6
  • Gale, S. A., Acar, D., & Daffner, K. R. (2018). Dementia.

    The American Journal of Medicine

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    131

    (10), 1161-1169. doi: 10.1016/j.amjmed.2018.01.022
  • Hutten, N.R.P.W., Mason, N.L., Dolder, P.C., & Kuypers, K.P.C. (2019) Motives and Side-Effects of Microdosing With Psychedelics Among Users.

    International Journal of Neuropsychopharmacology

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    22

    (7), 426-434. doi: 10.1093/ijnp/pyz029
  • Kaup, A. R., Byers, A. L., Falvey, C., Simonsick, E. M., Satterfield, S., Ayonayon, H. N., …Yaffe, K. (2016) Trajectories of depressive symptoms in older adults and risk of dementia.

    JAMA Psychiatry

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    73

    (5), 525–531. doi: 10.1001/jamapsychiatry.2016.0004
  • Lee M. A. & Shlain B. (1992). Acid Dreams: The Complete Social History of LSD: The CIA, The Sixties, and Beyond. In: Rev. Evergreen (ed). New York, NY: Grove Weidenfeld.
  • Luna, L. E. (2011). Indigenous and mestizo use of ayahuasca. In: The Ethnopharmacology of Ayahuasca. Kerala, India: Transworld Research Network.
  • McNamara, J.D. (2011). The Hidden Costs of America’s War on Drugs.

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    http://journal.apee.org/index.php?title=Spring2011_6
  • Nichols, D. E. (2016). Psychedelics.

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    (2): 264-355. doi: 10.1124/pr.115.011478
  • Otte, C., Gold, S. M., Penninx, B. W., Pariente, C. M., Etkin, A., Fava, M., … Schatzberg, A. F. (2016). Major depressive disorder.

    Nature Reviews Disease Primer

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    : 16065. doi: 10.1038/nrdp.2016.65
  • Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., … Ajaújo, D. B. (2019). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

    Psychological Medicine

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    49

    (4), 655-663. doi:10.1017/S0033291718001356
  • Prochazkova, L., Lippelt, D. P., Colzato, L. S., Kuchar, M., Sjoerds, Z., & Hommel, B. (2018). Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting.

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  • Reisberg, B., Ferris, S.H., de Leon, M.J., & Crook, T. (1982). The global deterioration scale for assessment of primary degenerative dementia.

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    , NY: The Haworth Press, 165-173.
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Psychedelics as Treatment for Depression in Patients with Dementia

Literature Review


Older adults

Aging is an inevitable part of life. Approximately 20% of the population in developed countries is comprised of adults over 60 years old (Wick, et al., 2000). The average life expectancy continues to grow meaning the risk of an individual developing an age-related disease also continues to grow (Clarfield, 2017). Future research should investigate how to prevent or cure age-related diseases.


Depression in older adults.

The American Psychiatry Association (APA) defines major depressive disorder as when at least five of the following nine symptoms are present: sadness, disinterest, weight changes, sleeping pattern changes, delayed cognition, tiredness, self-loathing, inability to concentrate, or reoccurring thoughts of suicide (2013a). Depression is not a normal part of getting older, although aging increases the risk of an individual developing depression (Blazer, 2003). Depression in older adults should be treated as any other mood disorder because complications may arise if the depression is left untreated. The Geriatric Depression Scale (GDS) serves to quantify the severity of depression in older persons by assessing mood, self-esteem, and energy (Sheikh & Yesavage, 1986). The shorted version of the GDS is used for patients with poor attention-spans such as those with dementia. This scale is not specifically for older persons with cognitive impairment. Consequently, it may not be a completely accurate assessment for patients with dementia.


Dementia in older adults.

Dementia can be the result of several medical conditions such as Alzheimer’s disease, Parkinson’s disease, and Lewy-body dementia (Gale, Acar, & Daffner, 2018). The World Health Organization estimates that 50 million people live with some form of dementia with 60-70% of cases attributed to Alzheimer’s disease (World Health Organization [WHO], 2019). Slightly different symptoms are present depending on the disease. The APA defines dementia as a neurocognitive disorder diagnosed when the following symptoms are present: poor attention-span, mal-orientation, fluctuation in disturbances, cognitive decline, and evidence of a physiological cause (2013b). The Global Deterioration Scale (GDS) defines stages that correlate with the severity of a patient’s cognitive decline by assessing memory, mood, behaviors, and activities of daily living (Reisberg, et al., 1982). Severe cognitive decline significantly decreases a person’s quality of life and complicates preexisting mental disorders. The comorbidity of dementia and depression can have severe and complex outcomes.


Depression and dementia.

Depression in older adults is a strong indicator of the early stages of dementia (Kaup et al., 2016). The symptoms of depression often continue while the dementia disease progression. An estimated 10-30% of people living with dementia also suffer from depression (Devanand et al., 1997). The Cornell Scale for Depression in Dementia (CSDD) scores the severity of depression specifically for patients with dementia by assessing mood-related signs, behavioral disturbances, physical signs, cyclic functions, and ideational disturbances (Alexopoulos, et al., 1988). The combination of depression and dementia often manifests into agitation and hostility (Volicer, 2018). These behaviors can make it difficult for caregivers to provide proper care to older adults suffering from both depression and dementia. Trials of antidepressants are currently the recommended treatment for older adults with depression and dementia despite the high risk of adverse effects (Ford & Almeida, 2017). A new depression symptom-relief medication could allow caregivers to provide proper care without the adverse effects of current antidepressants.


Psychedelics

Psychedelics are a class of drugs that increases serotonin levels and consequently alters mood, perception, and cognitive processes (Nichols, 2016). The side-effects of increased serotonin levels make psychedelics desirable to some people. Psychedelics are commonly consumed either religiously or recreationally (Luna, 2011), but small doses can improve cognitive abilities (Prochazkova et al., 2018). Future research may reveal the full potential of using psychedelics to treat mood disorders. The general use of psychedelics is controversial: some religious groups view psychedelics as a way to enhance their spirituality (Luna, 2011) while other religious groups condemn all recreational drug use (McNamara, 2011). This is the basis for the debate on the legality of psychedelics. Many countries, including the United States, classify psychedelics as illegal controlled substances (United States Code, 2016). Research is greatly limited due to the legal status of psychedelics.


History.

Some American religious groups in the early twentieth century encouraged the association of drugs with immoral behaviors (McNamara, 2011). The Harrison Anti-Narcotic Act of 1914 constitutionally enabled the federal government to regulate controlled substance (Terry, 1915), state legislations began classifying psychedelic-related crimes as felony offenses in 1966 (Lee & Shlain, 1987), and the 1970 Control Substances Act categorized psychedelics as schedule I drugs (United States Code, 2016). All of this legislation restricted the accessibility of psychedelics. Additionally, controlled substances with no medicinal benefit and a high risk for abuse are classified as schedule I drugs (United States Drug Enforcement Administration [DEA], n.d.), so psychedelic research was significantly reduced for a few decades (Carhart-Harris & Goodwin, 2017). The United States Drug Enforcement Administration (DEA) significantly increased the approval rate for research regarding schedule I drugs in 2017 (2018). The increased accessibility to psychedelic research could develop clinical use for medicinal benefits.


Dimethyltryptamine (DMT).

DMT is a psychedelic associated with strong hallucinogenic effects (Cakic, Potkonyak, & Marshall, 2010). Some people recreationally use DMT for a powerful psychological experience with a low risk of adverse effects (Davis, et al., 2018). The production of the spiritual brew, ayahuasca, commonly includes the plant

Psychotria viridis

which contains DMT (Domínguez-Clavé et al., 2016). Ayahuasca has been used in religious ceremonies throughout the upper Amazon for centuries (Luna, 2011). This sacred view of DMT’s psychological effects suggest a higher benefit to risk ratio.

Case studies have shown that, while uncommon, DMT can induce psychosis (Dobkin de Rios & Rumrrill, 2018) (Paterson, Darby, & Sandhu, 2015). The possibility of dramatic adverse effects is reason to proceed research with caution. Many observational studies have been conducted to investigate the current uses of DMT. A fewer number of controlled experiments have been performed to directly test the effects of DMT in a monitored setting.


Microdosing psychedelics for depression.

The term

microdosing

refers to the regularly scheduled consumption of very small dosages of some drug. Microdoses of psychedelics are typically ten to twenty times smaller than a recreational dose (Kuypers, et al., 2019). A microdose is usually too small to cause noticeable hallucinogenic effects. The microdose will cause an increase in serotonin levels resulting in some less intense side-effects. Approximately 20% of microdosers have experienced some acute adverse effects (Hutten, et al., 2019). The risks and benefits of any drug must be assessed before clinical usage. Microdoses of DMT had an antidepressant effect on rats without increasing anxiety (Cameron, et al., 2019). This evidence suggests that microdoses of DMT could be used clinically to ease symptoms of depression.

Current antidepressants may take up to several weeks before becoming fully effective (Otte et al., 2016). Waiting several weeks for symptom relief may feel distressing for a person with depression. Additionally, the first antidepressant trial fails for about 30% of depression cases leading to a long trial-and-error period (Conway et al., 2017). Being subjected to many failed medications may be disheartening for people suffering from chronic depression. Ayahuasca can be utilized as a fast-acting medication for treatment-resistant depression (Palhano-Fontes et al., 2019). Utilizing psychedelics as antidepressants could change the way psychiatrists treat depression.


Psychedelics effect in older adults.

There is not much evidence that psychedelics are beneficial specifically for older adults. Small doses of cannabis do not cause any significant effects in older adults with dementia (Van den Elsen, et al., 2015). The absence of any results includes the absence of adverse results. The clinical use of psychedelics has proven to be safe enough to begin research with larger doses.


Current Study

The recent increase in studies concerning the medicinal benefit of psychedelics could lead to a breakthrough in how depression is treated. This potential medication could also be useful in specifically treating depression in older adults with dementia. This experimental study explores the direct effect that microdoses of DMT have on treating depression in older adults with dementia. Prior studies suggest that microdoses of DMT can relieve symptoms of depression (Cameron, et al., 2019) (Palhano-Fontes et al., 2019). Some case studies warn researchers of the risk of psychedelic induced psychosis (Dobkin de Rios & Rumrrill, 2018) (Paterson, Darby, & Sandhu, 2015). Another study demonstrated the low risk of adverse effects of microdoses of psychedelics in older adults with dementia (Van den Elsen, et al., 2015). These studies together suggest the potential benefit of microdoses of DMT on depression symptom relief for older adults with dementia.


References

  • Alexopoulos, G.S., Abrams, R.C., Young, R.C., & Shamoian, C.A. (1988). Cornell Scale for Depression in Dementia.

    Biological Psychiatry

    ,

    23

    (3), 271-284. doi: 10.1016/0006-3223(88)90038-8
  • American Psychiatry Association [APA]. (2013a).

    Diagnostic and statistical manual of mental disorders

    , (5th ed.). Depressive Disorders. doi: 10.1176/appi.books.9780890425596.dsm04
  • American Psychiatry Association [APA]. (2013b).

    Diagnostic and statistical manual of mental disorders

    , (5th ed.). Neurocognitive Disorders. doi: 10.1176/appi.books.9780890425596.dsm17
  • Blazer, D.G. (2013). Depression in Late Life: Review and Commentary.

    The Journals of Gerontology: Series A

    ,

    58

    (3), M249-M265. doi: 10.1093/gerona/58.3.M249
  • Cakic, V., Potkonyak, J., & Marshall, A. (2010) Dimethyltryptamine (DMT): Subjective effects and patterns of use among Austrailian recreational users.

    Drug and Alcohol Dependence

    ,

    111

    (1-2), 30-37. doi: 10.1016/j.drugalcdep.2010.03.015
  • Cameron, L.P., Benson, C.J., DeFelice, B.C., Fiehn, O., & Olson, D.E. (2019). Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents.

    ACS Chemical Neuroscience

    ,

    10

    (7), 3261-3270. doi: 10.1021/acschemneuro.8b00692
  • Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N,N-Dimethyltryptamine.

    Brain Research Bulletin

    ,

    126

    (Pt. 1), 74-88. doi: 10.1016/j.brainresbull.2016.04.016
  • Carhart-Harris, R. L., & Goodwin, G. M. (2017). The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future.

    Neuropsychopharmacology

    ,

    42

    (11), 2105-2113. doi: 10.1038/npp.2017.84
  • Clarfield, A.M. (2018). Healthy Life Expectancy Is Expanding.

    Journal of the American Geriatrics Society

    ,

    66

    (1), 200-201. doi: doi.org/10.1111/jgs.15165
  • Conway, C. R., George, M. S., & Sackeim, H. A. (2017). Toward an evidence-based,operational definition of treatment-resistant depression: when enough is enough.

    JAMA Psychiatry

    ,

    74

    (1), 9–10. doi: 10.1001/jamapsychiatry.2016.2586
  • Davis, A.K., Barsuglia, J.P., Lancelotta, R., Grant, R.M., & Renn, E. (2018). The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption.

    Journal of Psychopharmacology

    ,

    32

    (7), 779-792. doi: 10.1177/0269881118769063
  • Devanand, D. P., Jacobs, D. M., Tang, M., Castillo-Castaneda, C., Sano, M., Marder, K., … & Stern, Y. (1997). The Course of Psychopathologic Features in Mild to Moderate Alzheimer Disease.

    Archives of General Psychiatry

    .

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