NOVA Health Recovery Ketamine Infusion Center Fairfax, Virginia
Call us at 703-844-0184 for more information
Contact us at NOVA Health Recovery Ketamine Center for more information or to schedule a consultation and infusion. No referral is necessary. Call 703-844-0184 or email us at email@example.com. You can also use the form below:
Scopolamine and Ketamine as Rapid Acting Antidepressants
Approximately one-third of patients with Major depressive disorder (MDD) fail to respond to first-line antidepressants. There is a need for rapid acting antidepressants. Two different classes of rapid acting antidepressants include ketamine, a non-competitive antagonist at the glutamate N-methyl-D-aspartate (NMDA) receptor and scopolamine, a non-selective acetylcholine muscarinic receptor antagonist. Scopolamine has demonstrated rapid antidepressant effects in MDD and bipolar patients.
Scopolamine is derived from Brugmansia, a flowering plant in the family of Solanaceae. The common name is Angel’s Trumpets. These plants are rich in alkaloids, in particular scopolamine, which in excess can cause amnesia, delirium, and anticholinergic syndrome.
By Paul K from Sydney – Brugmansia bicolor, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=17868322
The pursuit of rapid acting antidepressant research led to research of scopolamine infusions and intramuscular scopolamine injections for depression:
1991: Gillin administered intramuscular scopolamine for depression, with resulting improvement of depression but with a statistical non-significant effect.
2006: Drevets and Furey did several randomized double-blind trials demonstrating that depressed and bipolar patients had rapid antidepressant effects based on improvements in the MADRS score (Montgomery-Asberg Depression Rating Scale) by three days after the infusion. The effect was such that 2/3 of patients had marked improvement in depression with half having remission of depression. The treatment effect lasted over two weeks.
Key Papers regarding scopolamine are listed below:
Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA Jr. Potential of pretreatment neural activity in the visual cortex during emotional processing to predict treatment response to scopolamine in major depressive disorder. JAMA Psychiatry. 2013;70:280–90.
Khajavi D, Farokhnia M, Modabbernia A, et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012;73:1428–33.
Ketamine has a robust antidepressant effect, especially when added to existing antidepressant treatment. One study augmenting escitalopram (Celexa) with a single ketamine infusion demonstrated a 92% response rate (vs 51% without ketamine) and a depression remission rate of 76% (versus 14% without ketamine). Scopolamine affects similar mechanisms of action as does ketamine in reducing depression and anxiety.
The study by Furey and Drevets in 2006 demonstrated that three scopolamine infusions 3-5 days apart at 4mcg/kg IV over twenty minutes demonstrated robust antidepressant and antianxiety effects of scopolamine IV.
How does this work?
- The cholinergic system is involved in the pathophysiology of mood disorders and that depressed individuals may have excess cholinergic tone as seen when physostigmine (an anticholinergic inhibitor that increases cholinergic tone) rapidly increases depression and reverses mania into depression. Thus, blocking the cholinergic system may have antidepressant and anti-anxiety effects.
- Muscarinic (increased cholinergic tone) is more pronounced in depressed patients and when given muscarinic agonists, depressed patients have exaggerated responses on polysomnography and in neuroendocrine testing.
- There are genetic associations with muscarinic receptor gene polymorphisms being associated with increased depression as in the CHRM2 gene (also associated with alcoholism).
- Animals bred for increased muscarinic sensitivity demonstrated behaviors of depression such as reduced self-stimulation, lethargy, and behavioral despair (shown in a forced-swim test) when given muscarinic agents.
- Elevated cholinergic function may be a causal factor in mood disorders.
Tricyclic antidepressants do have antimuscarinic effects but also have a lot of side effects. Part of their efficacy in depression may be the anticholinergic effects that they have. Amitriptyline has a large occupancy of serotonergic receptor sites at traditional dosing and may explain why it is more efficacious than SSRI’s.
The dosing administration of scopolamine was determined by EEG effects in healthy volunteers. In this study, 10 volunteers were modeled with 0.5 mg IV scopolamine hydrobromide over 10 minutes. IM availability was only 57%. The 0.5 mg IV dose over 15 minutes represented the ideal dosing based on EEG outcomes.
The 2006 Furey and Drevets study utilized 15-minute infusions of scopolamine hydrobromide every 3-5 days for three sessions at 2.0, 3.0, and 4 mcg/kg dosing. The best results were at 4 mcg/kg dosing over 15 minutes resulting in a 50% decrease in the MADRS depression scoring by the fourth infusion. Two sets of study designs were done, and they demonstrated rapid improvement of depression and thus suggested hyperactivity of the cholinergic system as the cause of depression in some cases. There was no real effect on cognition by the infusions in terms of delirium or memory-related issues. The effect size of the infusions was larger than traditional antidepressant studies and the scopolamine infusions results in prolonged effects. Further studies reproduced the antidepressant effect of scopolamine infusions.
Because there is a delay before the onset of the antidepressant effect of scopolamine, it is felt there is gene transcription rather than a direct effect on the muscarinic receptors that makes it work. There are also areas in the brain that the NMDA receptor expression is regulated by muscarinic receptor stimulation (I,e, NMDAR types 1A and Type 2A) The efficacy of scopolamine may also be due to its interaction at a specific type of Muscarinic receptor (I.e. M3) as another study did not show glycopyrrolate and biperidin to be antidepressant even though they are anti-muscarinic.
Recent studies have demonstrated that the rapid-acting antidepressant effects of scopolamine, a muscarinic receptor antagonist, are also associated with increased glutamate transmission and synapse formation. Ketamine and scopolamine both have effects by increasing extracellular glutamate, elevating BDNF, activation mTORC1, and increasing the number of synapses (synaptogenesis) in the prefrontal cortex (PFC). Scopolamine and ketamine both antagonize inhibitory interneurons in the LFC to promote the antidepressant responses. Both NMDA and muscarinic acetylcholine receptor antagonism on the interneurons of the PFC are targets of rapid antidepressant agents. Increased synapse number and function in the PFC in response to ketamine or scopolamine reverses the pathophysiology associated with stress and depression which result in synaptic dysfunction. Changes in gene expression and synaptic plasticity are key features to scopolamine and ketamine’s effect on depression as reviewed in Zarate and Drevets 2013. The basis for the synaptic plasticity also involves mTORC1 activation and the production of proteins such as BDNF, which promotes dendritic spine formation. In depression and stress, there is a destruction of dendritic spines.
- Alterations of signaling pathways and neuroplasticity correlate with behavior changes and mood elevation with the use of ketamine and scopolamine. Chronic stress destroys synaptogenesis and dendritic spines.
- The volume and connectivity of the subgenual PFC and cingulate cortex is decreased in depressed individuals and there is a reduction in cell body size as well as a loss of synapses in the dorsolateral PFC. This results in a functional dysconnectivity in the brain of depressed individuals. There is also a dysregulation of genetic functioning as well in genes related to glutamate signaling.
- A region of interest in MDD is the hippocampus (HPC), which plays a key role in cognitive functions such as spatial and declarative memory and anxiety, as well as in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. HPC volume is reduced in depressed individuals and antidepressant therapy has been shown to reverse this stress-induced atrophy.
- There is a decreased number and length of apical dendrites in CA3 pyramidal neurons of the HPC and reduced synaptic connectivity in response to chronic stress in models of depression. Chronic stress destroys neural networks in the brain.
- Animal models demonstrate reduced length and branching of the apical dendrites in the PFC in response to chronic stress. Also seen are dendritic branching changes and decreased spine density in depression. In Ketamine and scopolamine treatment, pyramidal neurons in the PFC show enhanced number and function of dendritic spines (link)
- The amygdala, a subcortical structure involved in emotional memory formation and retrieval, has primarily been studied for its role in fear conditioning and memory. The amygdala exhibits a dysfunctional activity profile in individuals suffering from depression and anxiety.
- Depression should be considered a system-wide disorder, but the PFC is important as it receives and sends substantial projections throughout the brain to both cortical and subcortical regions that have been implicated in depression.
- Scopolamine and ketamine work through stimulation of mTORC1 signaling which promotes protein formation and synaptic spine formation. Synaptic spines are depleted in depression and stress. Rapamycin blocks mTORC1 and its use blocks ketamine and scopolamine’s behavioral and synaptic actions. Thus, mTorC1 is critical to the antidepressant actions of ketamine and scopolamine.
- The key event for mTORC1 activation is extracellular glutamate being released in the PFC
- Acute NMDA and muscarinic acetycholine (mACH) receptor antagonism are what produces the rapid glutamate burst in the PFC.
- Interneurons releasing the inhibitory neurotransmitter γ-aminobutyric acid (GABA) play an important role in mediating glutamate release from pyramidal cells which utilize mostly excitatory glutamate as the neurotransmitter. The interneurons tonically inhibit the glutamate burst. Ketamine and scopolamine turn off this interneuron to allow for the glutamate burst.
- Ketamine and scopolamine antagonize specific receptor subtypes on inhibitory interneurons that lead to disinhibition of glutamatergic pyramidal neurons causing a subsequent glutamate burst in the PFC – Ketamine and scopolamine turn off the interneuron so that the synapse can fire its glutamate burst
- An infusion of scopolamine increases extracellular glutamate in the striatum
- Despite the role of acetylcholine as a critical neuromodulator recent studies show that mACh receptors in the PFC may not have a prominent role in the direct excitation of cortical pyramidal neurons
- Evidence indicates that M1-ACh receptors modulate both cortical pyramidal and interneuron activity. Specific interaction by scopolamine with the M1-ACH is what makes it effective.
- Glutamate elevation requires low levels of Ketamine (10 mg/kg or less) and scopolamine (25 mcg/kg)
- The increased glutamate burst resulting from ketamine and scopolamine in the PFC leads to AMPA receptor activation and inward calcium currents to ultimately produce BDNF (Brain Derived Neurotrophic Factor)
- BDNF is released into the synapse to activate TRkB (tyrosine kinase B) which activates AKT and mTORC1 inside the postsynaptic neuron.
- This leads to protein production, increase dendritic spines, increased synaptogenesis and less depression = neuroplasticity
- mice lacking M1- or M2-ACh receptor do not show antidepressant responses following scopolamine treatment
- Link 2
- Does oral scopolamine work for depression? There is research regarding this as well as a double-blind randomized trial that enrolled 20 patients and used scopolamine 0.5 mg with citalopram (20-40 mg) for 6 weeks which showed a 74% reduction in the HAM-D (a depression ranking system) scores with scopolamine and citalopram combination treatment versus the citalopram-only group having a 59% decrease in depression. Likewise, the scopolamine augmentation was faster and seen by day 4. Oral scopolamine also can be added to a beta blocker to help with anxious depression as well.
- Infusions of Scopolamine can be useful in the context of ketamine infusions as a rapid acting antidepressant
- Scopolamine results in the production of synapses and neuroplasticity through a similar mechanism that ketamine works.
- The infusions of scopolamine are shorter and have no psychomimetic effect and can be used prior to ketamine infusions with excellent effect as they are anti-emetic, anti-anxiety, and antidepressant in nature.
- At NOVA Health Recovery Ketamine Infusion Center in Alexandria, Virginia, we treat patients with anxious depression, general anxiety, and bipolar disorder with scopolamine and ketamine infusions to maximize recovery. Contact us today at 703-844-0184 or here.
NOVA Health Recovery is a Ketamine Treatment Center in Fairfax, Virginia (Northern Virginia Ketamine) that specializes in the treatment of depression, anxiety, bipolar disorder, OCD, and chronic pain such as CRPS, cluster headaches, and fibromyalgia using Ketamine therapies, both infusion and home-based ketamine nasal spray and oral tablets. We also offer addiction treatment services with Suboxone, Vivitrol, and Sublocade therapies for opiate addiction as well as alcohol treatment regimens. Contact us at 703-844-0184 or at this link: NOVA Health Recovery Ketamine Infusion Center Near me Ketamine Infusion
Ketamine Provider | Ketamine near me | Psychedelic assisted therapy | Mushrooms | Ketamine assisted psychotherapy | Ketamine psychedelic therapy | KAP | K hole | New depression Treatments | Areas we serve:
Bethesda 20814 – Bethesda 20816 – Bethesda 20817 – Chevy Chase 20815 – Colesville 20904 – Cabin John 20815 – Glen Echo 20812 – Gaithersburg 20855 – Gaithersburg 20877- Gaithersburg 20878 – Gaithersburg 20879 – Garrett Park 20896 – Kensington 20895 – Montgomery Village 20886 – Olney 20830 – Olney 20832 – Potomac 20854 – Potomac 20859 – Rockville 20850 – Rockville 20852 – Rockville 20853 – Silver Spring 20903 – Silver Spring 20905 – Silver Spring 20906 – Silver Spring 20910 – Takoma Park 20912 – Wheaton 20902
Crestwood 20011- North Capitol Hill 20002 – Cathedral Heights 20016 – American University Park 20016 – Columbia Heights 20010 – Mount Pleasant 20010 – Downtown 20036 – Dupont Circle 20009 – Logan Circle 20005- Adams Morgan 20009 – Chevy Chase 20015 – Georgetown 20007 – Cleveland Park 20008 – Foggy Bottom 20037 – Rock Creek Park – Woodley Park 20008 – Tenleytown 20016
McLean 22101- McLean 22102 – McLean 22106 – Great Falls 22066 – Arlington 22201 – Arlington 22202 – Arlington 22203 – Arlington 22205 – Falls Church 22041 – Vienna 22181 – Alexandria 22314 – 22308 -22306 -22305 -22304 Fairfax – 20191 – Reston – 22009 – Springfield – 22152 22015 Lorton 22199
2303 – 22307 – 22306 – 22309 – 22308 22311 – 22310 – 22312
22315 -22003 – 20120 – 22015 – 22027 20121 – 22031 – 20124
22030 – 22033 – 22032 – 22035 – 22039 22041 – 22043
22042 – 22046 – 22044 – 22060 – 22066 20151 – 22079 – 20153 – 22101
22102 – 20171 – 20170 – 22124 – 22151 22150 – 22153
22152 – 20191 – 20190 – 22181- 20192 22180 – 20194 – 22182
Woodbridge – 22191 – 22192 -22193 -22194 – 22195
Springfield – 22150 – 22151 -22152-22153-22154-22155 -22156 – 22157 -22158 -22159 -22160 – 22161
Front Royal 22630
Warren County 22610 22630 22642 22649
Fredericksburg Va 22401 22402 – 22403 – 22404 -22405 -22406 -22407 -22408 – 22412
Please call Sendi Hair Loss Center now at 703-574-0974 for quality Hair Restoration services in Alexandria, VA.
20105 Aldie Loudoun County 20106 Amissville Culpeper County 20107 Arcola Loudoun County
20108 Manassas Manassas City 20109 Sudley Springs Prince William County
20109 Manassas Prince William County 20110 Manassas Manassas City
20111 Manassas Prince William County 20111 Manassas Park Prince William County
20112 Manassas Prince William County 20113 Manassas Park Manassas Park City
20115 Marshall Fauquier County 20116 Marshall Fauquier County
20117 Middleburg Loudoun County 20118 Middleburg Loudoun County
20119 Catlett Fauquier County – 20120 Sully Station Fairfax County
20120 Centreville Fairfax County – 20121 Centreville Fairfax County
20122 Centreville Fairfax County – 20124 Clifton Fairfax County
20128 Orlean Fauquier County -20129 Paeonian Springs Loudoun County
20130 Paris Clarke County
20131 Philomont Loudoun County 20132 Purcellville Loudoun County
20134 Hillsboro Loudoun County 20134 Purcellville Loudoun County
20135 Bluemont Clarke County 20136 Bristow Prince William County
20137 Broad Run Fauquier County 20138 Calverton Fauquier County
20139 Casanova Fauquier County 20140 Rectortown Fauquier County
20141 Round Hill Loudoun County 20142 Round Hill Loudoun County
20143 Catharpin Prince William County
20144 Delaplane Fauquier County20146 Ashburn Loudoun County
20147 Ashburn Loudoun County 20148 Brambleton Loudoun County
20148 Ashburn Loudoun County 20151 Chantilly Fairfax County
20151 Fairfax Fairfax County 20152 South Riding Loudoun County
20152 Chantilly Loudoun County 20152 Fairfax Loudoun County
20153 Chantilly Fairfax County 20153 Fairfax Fairfax County
20155 Gainesville Prince William County 20156 Gainesville Prince William County
20158 Hamilton Loudoun County 20159 Hamilton Loudoun County
20160 Lincoln Loudoun County 20160 Purcellville Loudoun County
20163 Sterling Loudoun County 20164 Sterling Loudoun County
20165 Potomac Falls Loudoun County 20165 Sterling Loudoun County
20166 Dulles Loudoun County 20166 Sterling Loudoun County
20167 Sterling Loudoun County 20168 Haymarket Prince William County
20169 Haymarket Prince William County 20170 Herndon Fairfax County
20171 Oak Hill Fairfax County 20171 Herndon Fairfax County
20172 Herndon Fairfax County 20175 Leesburg Loudoun County
20176 Lansdowne Loudoun County 20176 Leesburg Loudoun County
20177 Leesburg Loudoun County 20178 Leesburg Loudoun County
20180 Lovettsville Loudoun County 20181 Nokesville Prince William County
20182 Nokesville Prince William County 20184 Upperville Fauquier County
20185 Upperville Fauquier County 20186 Warrenton Fauquier County
20187 New Baltimore Fauquier County 20187 Vint Hill Farms Fauquier County 20187 Warrenton Fauquier County
20188 Vint Hill Farms Fauquier County 20188 Warrenton Fauquier County
20190 Reston Fairfax County 20190 Herndon Fairfax County
20191 Reston Fairfax County 20191 Herndon Fairfax County
20194 Reston Fairfax County 20194 Herndon Fairfax County
20195 Reston Fairfax County 20195 Herndon Fairfax County
20197 Waterford Loudoun County 20198 The Plains Fauquier County
Loudoun County, VA – Standard ZIP Codes