***Be gentle folks...this is my first Noot write-up (with more to come), and I'm open to suggestions on how to structure these and/or make them better, and will entertain requests for specific Noots***Huperzine-A
Huperzine-A (often abbreviated as Hup-A) is a compound derived from the Huperziceae family of herbs.
Hup-A is known as an acetylcholinesterase inhibitor, meaning that Hup-A prevents acetylcholine from being broken down by enzymes. The net result of this is that acetylcholine levels rise (1)
2. Quick Tips:
a. Hup-A is water soluble (no need to take with food)
b. Initial effect/spike is quick
c. Half-life can range from 14 – 28.5 hours
a. Memory enhancement (9)
b. Increased alertness (8)
c. Enhanced sensory perceptions (8)
d. Improved learning capacity
e. Neuro-protective (2,3,4)
f. Neurogenesis (5)
g. Somatostatin inhibitor via ACh (12, 13) > resulting in higher Growth Hormone levels/secretion
4. Known Pharmacology:
Blood plasma levels tend to spike quickly with oral application, ranging from 15min or less and peaking around 1 hour post ingestion (6, 7).
5. Safety Profile:
The NOAEL (No Observable Adverse Effects Limit) is postulated to be 1mg/kg for female rats, 3mg/kg for males rats, and 0.1mg/kg for canines. No toxicity data for humans currently exists. (other safety data found in source 11).
Considered to be relatively safe for humans. No major side effects were noted in clinical trials, though there are a number of anecdotal reports of sleep disturbances.
6. Dosing Protocol
a. Typical dosing ranges from 50-200mcg daily
b. Doses can be divided or taken all at once
c. Does not need to be taken with food
d. Typical cycle length is 2-6 weeks.
e. Optimal time “off” hup-a is not well established.
So what is acetylcholine?
Acetylcholine (or ACh for short) is a neurotransmitter involved in neural signaling in both the autonomic and peripheral nervous system, and motor division of the somatic nervous system (think activating muscles).
Acetylcholine is synthesized in certain neurons by the enzyme choline acetyltransferase from the compounds choline and acetyl-CoA, and is often called the “learning neurotransmitter.”
Acetylcholine and the Peripheral Nervous system:
As far as muscle contractions go, ACh accomplishes this by binding to receptors on skeletal muscle fibers, opening up sodium channels that initiates a cascade of events leading to muscle contractions.
Acetylcholine and the Autonomic Nervous System:
Acetylcholine is released from sympathetic and parasympathetic neurons and long story short, stimulates the release of adrenaline and norepinephrine (via the adrenal medulla).
Acetylcholine and the Central Nervous System: (this is what we are concerned with in regards to nootropic effects):
a. Acts mainly as a neuromodulator (regulator) of arousal, reward and plasticity (neural adaptability) (8).
b. Plays an important role in enhancing sensory perceptions, alertness and attention (8).
c. Inability or reduced capacity to produce ACh has been associated with memory decline and Alzheimer’s disease (9)
d. Promotes REM sleep (10)
1. Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine
2. Ved HS, et al Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate . Neuroreport. (1997)
3. Huperzine A regulates amyloid precursor protein processing via protein kinase C and mitogen-activated protein kinase pathways in neuroblastoma SK-N-SH cells over-expressing wild type human amyloid precursor protein 695
4. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine
5. Ma T, et al Huperzine A promotes hippocampal neurogenesis in vitro and in vivo . Brain Res. (2013)
6. Qian BC, et al Pharmacokinetics of tablet huperzine A in six volunteers . Zhongguo Yao Li Xue Bao. (1995)
7. Li YX, et al Pharmacokinetics of huperzine A following oral administration to human volunteers . Eur J Drug Metab Pharmacokinet. (2007)
8. Himmelheber, AM; Sarter, M; Bruno, JP (2000). "Increases in cortical acetylcholine release during sustained attention performance in rats". Brain research. Cognitive brain research 9 (3): 313–25. doi:10.1016/S0926-6410(00)00012-4. PMID 10808142.
9. Francis PT, Palmer AM, Snape M, Wilcock GK (February 1999). "The cholinergic hypothesis of Alzheimer's disease: a review of progress". J. Neurol. Neurosurg. Psychiatr. 66 (2): 137–47. doi:10.1136/jnnp.66.2.137. PMC 1736202. PMID 10071091.
10. Platt, Bettina; Riedel, Gernot (2011). "The cholinergic system, EEG and sleep". Behavioural Brain Research 221 (2): 499–504. doi:10.1016/j.bbr.2011.01.017. PMID 21238497.
11. Chemistry, Pharmacology, and Clinical Efficacy of the Chinese Nootropic Agent Huperzine A
12. Endocrinology. 1980 Jul;107(1):122-9. Acetylcholine inhibits the release of somatostatin from rat hypothalamus in vitro. Richardson SB, Hollander CS, D'Eletto R, Greenleaf PW, Thaw C.
13. J Clin Invest. 1996 Feb 15; 97(4): 934–940. doi: 10.1172/JCI118516 PMCID: PMC507138. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. C A Jaffe, R DeMott-Friberg, and A L Barkan