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“Smart” Drugs to Stimulate and Regenerate Your Brain
❖ Enhance memory and learning ability
❖ Protect neurons under oxygenation or chemical assault
❑ Cerebral ischemia, stroke
❑ Drugs, neurotoxins
❖ Increase neuronal efficiency
❖ Enhance focus and motivation
❖ Are relatively non-toxic
CaffeineStimulant and mood elevator
Described in ancient Chinese and Arabic texts
Goats consumed berries coffee plant
“Gamboled and frisked about all through the night instead of sleeping.” (2)
L-Theanine
Green tea extract
Tempers caffeine side effects
Esp. anxiety, insomnia, and BP elevation
Enhances Caffeine’s positive effects:
Improved speed and accuracy of performance, Reduced susceptibility to distracting information
Dose: 50 mg caffeine/ 100 mg L-theanine. (3)
Piracetam and Choline-GABA Derivative. Enhances memory formation. Choline enhances the effects of piracetam.
Dose: 1600 mg piracetam; 200-300 mg. choline.
Creatine-Improves short term memory, reasoning, and enhances oxygenation.Dose: Loading 20 gm/day, x 5 days then 5 gm/d.
Bacopa-Enhances focus and attention reduces anxiety and improves long term memory.
Dose 300 mg with a fat source (i.e., Ghee, Avocado, Coconut Oil)
Rhodiola-Improves mood enhances memory, reduces reaction time, improves reasoning skills.
Dose: 350 mg/day. 3 days on, 1 day off cycle.
Asian Ginseng-Improves memory and memory retention, enhanced attention and focused, reduces anxiety, enhances performance, reaction time, and endurance.
Dose: 100 mg/day
William Clearfield D.O.
NHIMA, Fall 2019
Executive Director
American Osteopathic Society of Rheumatic Diseases
✓ Two or more amino acids linked by a peptide bond in a chain
✓ Protein chains are > 50 A.A. Combinations
✓ Enables
✓ Growth
✓ Repair
✓Gives cells and body, shape
✓ Energy Source
❑ Structurally similar to proteins
❑ Contain < 50 amino acid chains.
❑ “Oligopeptides” < 20 A.A.
❑ “Polypeptides” 21-50 A.A.
❑ Sequence, shape, and type of amino acids involved determine a peptides’ function.
✓ 7000 known Peptide Sequences
✓ 500 with sort of therapeutic value
✓ 60 approved (FDA) as medications.
➢ Addresses:
➢ Immune Dysregulation
➢ Inflammation
➢ ROS
➢ Use in Combinations
Neuro-endo-immune Issues
TBI
Joint Injury
Infectious Dx
(Viral-HBV, HVC, CMV, EBV)
IBD-UC and Crohn’s
COPD, CF
Sleep
Memory
Depression/anxiety
Cognition
Cellular rejuvenation and
restoration
Pain relief.
❖ Hormones act on nuclear receptors
Activate genes
Synthesize proteins
❖ Peptides act on membrane receptors
Intracellular signaling
Cells “crosstalk”
❖ Peptide signaling creates more rapid response
Less Side effects
Epithalon
A 4 Amino Acid Peptide Designed to Delay Mortality
PT 141-Bremelanotide
Sexual Arousal Through Direct CNS Stimulation
Favorite Peptides
• Growth Hormone Mimetics– GHRH
• Semorelean• CJC 1295 +/- DAC
– GHRP• GHRP 2• GHRP 6• Ipamorelin• Hexarelin
• Immune Modulating Peptides– Thymosin Alpha 1 (TA1) (increases TH1)– Thymosin Beta 4 (Tβ4) (increases TH1/decreases TH2))– BPC-157 (decreases TH2/healing hormone) (oral, SQ, nasal, eye drops) “Homeostasis Peptide.”– Synergistic with pineal protein Epithalon
• Rejuvenation/Pain– BPC-157, TB4, Epithalon, DSIP, GHRH/GHRP
Favorite Peptides
• Brain peptides (memory, depression, anxiety, TBI, brain function, etc.)– Cerebrolysin– Semax– Selank– Synergistic with Epithalon, TB4, BPC-157, DSIP
• Sleep peptides– Epithalon “Homeostasis Peptide”– Delta sleep-inducing peptide (DSIP)– CJC/Ipamorelin (GHRH/GHRP) (other combo’s)– AOD
• Antimicrobial peptides– LL-37 (effective against Lyme cysts, viruses, fungal, parasites) (synergistic with TA1)
❖ Hormones
❖ Immune system
❖ Sleep
❖ Inflammatory cytokines
❖ Cell renewal
❖ Cancer cell destruction
❖ Libido
❖ Sexual arousal
❖ Weight loss
❖ Lean muscle gain
❖ Wound healing
❖ Brain function
❖ Urinary System
❖ Reproductive System.
PT 141-BremelanotideA “LITTLE BLUE PILL ALTERNATIVE”
Peptides
1. PT 141
2. Thymosin Beta 4
PT-141 Failed Sildenafil Study
• Study of failure of Sildenafil; Rx PT 141
• Randomized Double
• Blind Placebo controlled study
• N = 342 married men
• 10 mg PT-141 as an intranasal spray
• 45 minutes to 2 hours prior to sexual stimulation
• Minimum 16 doses/attempts
• PT-141 Patients had greater intercourse satisfaction (p=.03)
• Side Effects: Nausea, flushing, headache
• Diamond LE et al. Urology 2005;65(4): 755–9.
Peptides
1. PT 141
2. Thymosin Beta 4
Peptides
1. PT 141
2. Thymosin Beta 4
• PT 141 – 1000 mcg/ml
• ● 2 ml vial
• 1.75 mg sq prn
• 45 minutes before event
• Not > 1 dose/24 hours
• Not > 8 doses /month
• ● Libido can increase after 2-6 hours in
• Recommend trying it 12 hours before the event
• Careful mixing it with
• PDE 5 inhibitor- 12 hourerections can occur
• June 28, 2019
• Now FDA Approved!
Nirvana!FDA Approved: Vylessi
➢Premenopausal female sexual dysfunction
➢No indication for men or post-menopausal women
➢Not indicated for sexual performance issues
➢Contraindicated:
➢Uncontrolled HBP, CVD
➢Caution:
➢ <1% incidence of focal hyperpigmentation
➢Nausea on second dose. 13% discontinuation rate
• www.thepharmaletter.com/article/amag-pharma-closes-deal-for-northamerica- rights-to-rekynda
➢
Cerebrolysin
Semax
Selank
❖ Neuroplasticity
❖ Neuroregenerative
❖ Neuroprotective
❖ CNTF – Ciliary Neurotrophic Factor
❖ Counters the adverse effects of
elevated levels of fibroblast growth
factor (FGF-2)-scar formation.
❖ GDNF – Glial Cells Derived Neurotrophic
Factor
❖ IGF-1 - Insulin-like Growth Factor 1
❖ IGF-2 – Insulin-like Growth Factor 2
Dementia
CVA-Protective and Post Event
Traumatic Brain Injury
o Cerebrolysin-(30 ml/day, 5 days/ week)
o 147 patient, 4-week post CVA
o 200% in cognitive scores (MMSE) exam.
o ADL scores improved in 35% vs. control
o 85% pts. showing at some improvement.
o Regulates glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity.
o Decreased β-amyloid deposition /microtubule-associated protein tau phosphorylation
o Increases synaptic density and restores neuronal cytoarchitecture.
o Improved cognitive and behavioral performance
Vereshagin N V et al., 2001 Therapeutic Archives, 73:22-27
Masliah E. et al. / Drugs Today (Barc). 2012 Apr;48 Suppl A:3-24
Inhibits calpain, reduces apoptosis
➢ Treated patients recovered motor function in 20-21 days; untreated group 90 days to obtain the same level of service.
➢ Improved Cognitive Function
➢ Mortality Reduction with early Cerebrolysin intervention
Masliah E. et al. / Drugs Today (Barc). 2012 Apr;48 Suppl A:3-24.
Ever Neuro Pharma; Cerebrolysin Monograph, Unterach, Austria, 2010 chrome-extension://oemmndcbldboiebfnladdacbdfmadadm/https://nootropicspot.com/wp-content/uploads/2017/08/Cerebrolysin.pdf-54.
Ladumar, G et al., J. Neural Transm 2005; 112:415-428
Hong., et al. for the CASTA Investigators, International Journal of Stroke Vol 4., Oct 2009, 406-412.
Destructive chemokines, cytokines, and neuropeptides
Oxidative Stress Reduction
Neuroinflammation Modulation
Brain cell mitochondria destruction
Hong., et al. for the CASTA Investigators, International Journal of Stroke Vol 4.,
Oct 2009, 406-412.
28 days immediately post TBI injury
=
Cognitive performance No Rx. x 1 year.
1. Ever Neuro Pharma; Cerebrolysin
Monograph, Unterach, Austria, 2010
Ever Neuro Pharma; Cerebrolysin Monograph, Unterach, Austria, 2010 chrome-
extension://oemmndcbldboiebfnladdacbdfmadadm/https://nootropicspot.com/
wp-content/uploads/2017/08/Cerebrolysin.pdf-78
❑ Single dose up to 50 ml-multiple doses over a cycle preferred
❑ Treatment over 10-20 day course-Daily Dose
❑ After the initial course, reduce dose to 2-3 days/week
❑ A treatment “holiday” equal to the length of treatment is recommended every other cycle.
❑ IM injection-May give up to 5 ml
❑ IV Injection 10 ml undiluted-10 to 50 ml infuse in NSS in 15-60 minutes
❑ Vitamins and drugs may be mixed in IV solution, not in the syringe
Contraindications (19)
❖ Drug Hypersensitivity
❖ Epilepsy
❖ Severe Renal Impairment
Special Considerations (20)
▪ Do not mix with amino acid solutions
▪ Monitor anti-depressant and MAO inhibitors-dose may need to
be lowered
▪ Ever Neuro Pharma; Cerebrolysin Monograph, Unterach, Austria, 2010 chrome-
extension://oemmndcbldboiebfnladdacbdfmadadm/https://nootropicspot.com/wp-
content/uploads/2017/08/Cerebrolysin.pdf-78
Toxicity studies = 5 times human therapeutic dose for 26 weeks
No substance-related intolerability
No teratogenic, embryotoxic or foetotoxic effects
No antibody formations, no anaphylactic reactions
No carcinogenicity recorded
▪ Ever Neuro Pharma; Cerebrolysin Monograph, Unterach, Austria, 2010 chrome-
extension://oemmndcbldboiebfnladdacbdfmadadm/https://nootropicspot.com/wp-
content/uploads/2017/08/Cerebrolysin.pdf-78
o Organic Brain disorders, metabolic disorders, neurodegenerative disorders (dementia)
o 5 days/week x 4 weeks
o 2-4 cycles/year
o 10 ml/d cognition
o 30 ml/d behavior
o Post-apoplectic complications (Stroke)o 5 days/week up to 4 weeks
o Up to 20 days (acute)
o Treat ASAP
o 30-50 ml (Higher doses for more severe s/s5 days/week x 4 weeks for rehab
o 10-30 mk/d
o Craniocerebral Trauma 10-50 ml
o Children 1-2 ml
DosingAcute Brain Trauma
Dosage 30 ml–up to 50 ml for severe cases
Treatment cycle up to 20 days
Window Opportunity treatment starts as soon as
possible
Rehabilitation After Brain Trauma
Dosage 10 ml–up to 30 ml for severe cases
Treatment cycle 5 days per week/up to 4 weeks
Window Opportunity as soon as possible after the acute
treatment
ACTH/MSH-like analog peptide
✓ Neuroprotective
✓ Anxiolytic
✓ Antidepressant
✓ Analgesic
ACTH/MSH-like analog peptide
BDNF = serotonin, NE
Antidepressant, anti-anxiety
Encourages growth and differentiation of new neurons and synapses
Necessary for long term memory retention
Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM (March 1995). "A BDNF autocrine loop in adult sensory neurons prevents cell death." Nature. 374 (6521): 450–53. Bibcode:1995Natur.374..450A. doi:10.1038/374450a0. PMID 7700353.
Atsenko KA, Glazova NY, Inozemtseva LS, Andreeva LA, Kamensky AA, Grivennikov IA, Levitskaya NG, Dolotov OV, Myasoedov NF (November
2013). "Heptapeptide Semax attenuates the effects of chronic unpredictable stress in rats." Dokl. Biol. Sci. 453: 353–7.
ACTH/MSH-like analog peptide
➢ Memory
➢ Learning➢ Counters negative learning and memory effects of heavy
metals
➢ Attention➢ Relieves Symptoms of ADHD
➢
➢ Augments psychostimulants on central dopamine release
➢ Modulates brain development.
➢ Brain Health With Cerebrolysin And Other Peptides. (n.d.). Retrieved from https://agemed.org/wp-content/uploads/ONEIL-SMITH-Brain-Health-with-Cerbolysin-a
Indications:
❖ Anxiety/Depression
❖ Memory retention and learning❑ Increase in mental processing
❑ Improvement in memory recall
❖ Hypoxemic States❖ TIA, CVA (Stroke) and Acute MI
❖ Heavy Metal Toxicity
❖ Pain relief
Indications:
1. ADHD
1. Increased attention during repetitive tasks
2. Migraine Headache
3. Increased Intellectual capacity
4. Mental Clarity
5. Mood StabilizerImproves Outlook on life
6. No “high” feeling
Indications:
❖ Increased Energy
❖ Improved Visual Acuity
❖ Expanded visual fields
❖ Increased electrical sensitivity of optic nerve
❖ Improved color vision
❖ Improves olfactory sense
Infrequent Side Effect: Secondary Anxiety
300 mcg –1,000 mcg SubQ/ 1/day once daily
2 times weekly
More can lead to desensitization
Depends on patient response
Can alternate with Selank
Infrequent Side Effect: Secondary Anxiety
300 mcg –1,000 mcg SubQ/ 1/day once daily
2 times weekly
More can lead to desensitization
Depends on patient response
Can alternate with Selank
Infrequent Side Effect: Secondary Anxiety
1. Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM (March 1995). "A BDNF autocrine loop in adult sensory neurons prevents cell death." Nature. 374 (6521): 450–53. Bibcode:1995Natur.374..450A. doi:10.1038/374450a0. PMID 7700353.
2. Atsenko KA, Glazova NY, Inozemtseva LS, Andreeva LA, Kamensky AA, GrivennikovIA, Levitskaya NG, Dolotov OV, Myasoedov NF (November 2013). "Heptapeptide Semax attenuates the effects of chronic unpredictable stress in rats." Dokl. Biol. Sci. 453: 353–7.
3. Tsai SJ. Semax, an analog of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypo 2007;68(5):1146-6
4. Asmarin IP nezavibat VN, Miasoedor NF, et al. A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study). ZVNDIP 1997;47(2):420-30.
5. Brain Health With Cerebrolysin And Other Peptides. (n.d.). Retrieved from https://agemed.org/wp-content/uploads/ONEIL-SMITH-Brain-Health-with-Cerbolysin-a
6. http://ccrstandard.com/semax/, accessed July 13, 209
Anti-anxiety, Antidepressant, Opioid, Alcohol Withdrawal/Dependence
o Immunostimulatory peptide
o Located in the heavy chain of IgG
o Modulates:
✓ IL- 6
✓ 5-HTP, dopamine, and norepinephrine,
✓ T-helper cell cytokines
✓ Increases BDNF,
✓ Reduces the breakdown of enkephalins.
Benzodiazepines
01 Alters Affinity for GABA-A
Cell Receptor.
02 Potentiates GABA
03 Sedating
Addictive
Cognition Issues
Selank
01 Alters Affinity for GABA Cell
Receptor
02 Potentiates GABA Inhibition > than
Benzos
03 Non-sedating
Non-addictive
No cognition loss
1. ].Seredenin SB, Kozlovskaia MM, Blednov IuA, Kozlovskiĭ II, Semenova TP, Czabak-Garbacz R, Nezavibat'ko VN, MiasoedovNFZh, The anxiolytic action of an analog of the endogenous peptide tuftsin on inbred mice with different phenotypes of the emotional stress reaction.Vyssh Nerv Deiat Im I P Pavlova. 1998 Jan-Feb; 48(1):153-60.
2. Kolomin TA, Agapova TIu, Agniullin IaV, Shram SI, Shadrina MI, Slominskiĭ PA, Limborskaia SA, Miasoedov IF, Transcriptome alteration in the hippocampus under the treatment of tuftsinanalog Selank]. Zh Vyssh Nerv Deiat Im I P Pavlova. 2013 May-Jun; 63(3):365-74.
Increases intracellular antioxidant levels. (7)
Upregulates of BDNF and serotonin activates learning and memory. (5)
Adaptogenic properties; Environmental stressor. (6)
Increases blood flow to the brain. (8)
Decreases blood pressure
Selank inhibits mast cell activity rendering it useful in Mast Cell
Activity Syndrome (MCAS) and POTS. (12-13)
Selank exhibits a penchant for weight loss and lowers cholesterol versus a
control group. (10)
It increases lymph flow to the gastric lining, reducing stomach ulcer size. (11)
“Stacking” Selank with Semax enhances focus and concentration (14)
4. Phan RT, Saito M, Basso K, Niu H, Dalla-Favera R. BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat Immunol 2005;6(10):1054–60.
5. Semenova, TP, Kozlovskii, II, Zakharova, NM, Kozlovskaia, MM, “Experimental optimization of learning and memory processes by Selank,” Eksp Klin Farmakol. 2010 Aug;73 (8):2-5.
6. Uchakina ON, Uchakin PN, Miasoedov NF, Andreeva LA, Shcherbenko VE, MezentsevaMV, Gabaeva MV, Sokolov OIu, Zozulia AA, Ershov FI, [Immunomodulatory effects of Selank in patients with anxiety-asthenic disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-5. [Original article in Russian] Accessed from https://www.ncbi.nlm.nih.gov/pubmed/18577961, July 14, 2019
7. Fomenko EV1, Bobyntsev II2,3, Kryukov AA4, Ivanov AV1, Andreeva LA5, Myasoedov NF5. Effect of Selank on Functional State of Rat Hepatocytes under Conditions of Restraint Stress. Bull Exp Biol Med. 2017 Aug;163(4):415-418. doi: 10.1007/s10517-017-3817-8. Epub 2017 Aug 29.
8. Gan'shina TS, Kozlovskiĭ II. [Effects of the new peptide anxiolytic drug selank on the cardiovascular system functioning and respiration in cats]. [Article in Russian] Eksp KlinFarmakol. 2005 Jul-Aug;68(4):33-5.
9. Kolik LG1, Nadorova AV, Kozlovskaya MM. Efficacy of anxiolytic peptide selank during
modeling of a withdrawal syndrome in rats with stable alcoholic motivation. Bull Exp Biol
Med. 2014 May;157(1):52-5. doi: 10.1007/s10517-014-2490-4. Epub 2014 Jun 10.
10.Mjasoedov NF1, Andreeva LA, Grigorjeva ME, Obergan TY, Shubina TA, Lyapina LA. The
influence of Selank on the parameters of the hemostasis system, lipid profile, and blood sugar
level in the course of experimental metabolic syndrome. Dokl Biol Sci. 2014 Sep;458:267-70.
doi: 10.1134/S0012496614050020. Epub 2014 Nov 5.
11.Pavlov TS, Sanzhieva LTs, Samonina GE, Sergeev VI, Lelekova TV. [Effect of new synthetic
anxiolytic selank on gastric wall blood flow and mesenteric lymphatic vessels contractility in
anesthetized rats]. [Article in Russian] Ross Fiziol Zh Im I M Sechenova. 2005 Feb;91(2):178-
83.
12.T. Ganshina, I. Kozlovskii (2005) Effects of the new peptide anxiolytic drug selank on the
cardiovascular system functioning and respiration in
catshttps://www.ncbi.nlm.nih.gov/pubmed/16193654
13.Fedorowski A1,2, Li H3, Yu X3, Koelsch KA3,4, Harris VM3,4, Liles C3, Murphy TA3, Quadri
SMS3,4, Scofield RH3,4, Sutton R5, Melander O1, Kem DC3. Antiadrenergic autoimmunity in
postural tachycardia syndrome. Europace. 2017 Jul 1;19(7):1211-1219. doi:
10.1093/europace/euw154.
14.Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA.
[Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorg
Khim. 2001 May-Jun;27(3):180-3. Russian. PMID:11443939
➢ Anxiety➢ Depression➢ Chronic Fatigue➢ Adrenal Fatigue➢ Anti-viral activity➢ Anti-inflammatory activity
2-3 drops 0.15% intranasal spray 2-3 X/D
Refrigerate.
Side Effect: Rare, fatigue.
Class Pain Immunity Inflammation
Libido
Anti-Aging
Weight Loss Cognitive Antioxidant Sleep Dose Conditions
PT-141MSH
Analog+++ +
1-2 mg 2x/d
Libido, Weight Loss,
Tanning
GHRH/GHRPHGH
Mimic + + + + + ++
160-400mg @
hs
Healing, Body Fat,
Rejuvenation
Semax Nootropic + + ++ + +++ +++ ++ +100-300
mg/d
Cognitive Dysfunction,
Memory,
Selank Nootropic + + + ++ + ++100-300
mg/dDementia, Stroke, TBI
CJC/IpamorelinGHRP/GH
RH + + ++ + + ++150-300
mg/dGH
Stimulation
Peptide Summary
Class PainImmuni
tyInflammati
onLibid
oAnti-Aging
Weight Loss
Cognitive
Antioxidant Sleep Dose Conditions
Thymosin Alpha 1
TH 1 Stimulation + +++ ++ ++ + ++
50-300 mcg/d
Immune boost; CA, Infectons
Thymosin Beta 4
TH1/TH2 Balance ++ +++ +++ ++ ++ ++ +
50-300 mcg/d
Immune moduclation,
CA, Neurorejuvenation, muscle
pain
BPC 157Anti
inflammatory +++ +++ +++ +++ + + +++ +
Oral 500 mg 1-4/d/50-200 2/d
Wound healing,
orthopedic repair, GI Healing,
rejuvenation
EpithalonPineal Peptide
Gland + ++ ++ +++ ++ +++ +++ 50-150mg/d
Anti-biofilm, infections, Lyme, anti-bacterial, antibiotic, antiviral,
antiparasitic
The American Osteopathic Society of Rheumatic Diseases
OMED October 25-28, 2019 Baltimore Maryland
Congress of Medical Excellence 2.0
February 28, 29, March 1, 2020
Peppermill Resort
Reno, NV 89523
www.aosrd.org
570-881-6821
William Clearfield D.O.9550 S. McCarran Blvd.
Reno, NV [email protected]
570-881-6821
We are happy to help you!
